Yourlawyer.com (Bextra Lawsuit News)

Pfizer Geodon Whistleblower Represented by Parker Waichman Alonso LLP

Wed, 09 Sep 2009 00:00:00 -0700

A whistleblower who was involved in last week's record breaking $2.3 billion Pfizer settlement was represented by the Great Neck, NY law firm of Parker Waichman Alonso LLP. The whistleblower lawsuit alleged that Pfizer illegally promoted the off-label use of the antipsychotic medication Geodon.

"We are proud of our client and the other relators who stepped forward to expose Pfizer's wrongdoing, and helped to make this settlement possible," said David Krangle, an attorney with Parker Waichman Alonso LLP. "We are also proud that our firm was able to play a part in obtaining justice for American taxpayers."

The Parker Waichman Alonso lawsuit was one of nine settled by the U.S. Department of Justice that charged Pfizer illegally marketed Geodon, as well as the pain killer Bextra; Zyvox, an antibiotic; and Lyrica, an anti-epileptic drug. The civil settlement also resolves allegations that Pfizer paid kickbacks to health care providers to induce them to prescribe these, as well as other, drugs.

As we reported last week, the $2.3 billion settlement is the largest healthcare fraud settlement in the history of the U.S. Department of Justice. The Geodon portion of the settlement was $301 million.

Under the terms of the settlement, Pfizer subsidiary Pharmacia & Upjohn Company Inc. has also agreed to plead guilty to a felony violation that it illegally promoted the off-label use of Bextra. Pharmacia & Upjohn will pay $1.3 billion toward the total settlement.

Pfizer also has agreed to enter into an expansive corporate integrity agreement with the Office of Inspector General of the Department of Health and Human Services. That agreement provides for procedures and reviews to be put in place to avoid and promptly detect conduct similar to that which gave rise to this matter, the Justice Department said.

Whistleblower lawsuits are filed under the False Claims Act, a federal law that empowers people to file lawsuits against federal contractors claiming fraud against the government. Successful whistleblowers can receive a portion of the damages recovered. According to the Department of Justice, the whistleblowers involved in last week's Pfizer settlement will receive $102 million of the federal fines.

Pfizer's Illegal Promotion of Bextra and Other Drugs Results in Record Settlement, Guilty Plea

Thu, 03 Sep 2009 00:00:00 -0700

Pfizer Inc. and its subsidiary, Pharmacia & Upjohn Company Inc., have agreed to pay a record-setting $2.3 billion to settle claims arising from the illegal marketing of some drugs. According to a U.S. Department of Justice press release, Pharmacia & Upjohn Company has also agreed to plead guilty to a felony violation regarding off-label promotions of the painkiller Bextra. Bextra was withdrawn from the market in 2005.

As we've reported previously, doctors may prescribe Food & Drug Administration-approved medicines any way they see fit. But companies are legally barred from promoting unapproved, or so-called off-label, uses.

According to the Justice Department press release, Pharmacia & Upjohn Company will pay a criminal fine of $1.195 billion, the largest criminal fine ever imposed in the United States for any matter, for the Bextra promotions. Pharmacia & Upjohn will also forfeit $105 million, for a total criminal resolution of $1.3 billion. According to Reuters, Bextra had only been approved to treat two types of arthritis pain and uterine pain, but the government claims it was marketed as a treatment for all types of pain.

In addition, Pfizer has agreed to pay $1 billion to resolve allegations it illegally promoted Bextra; Geodon, an anti-psychotic drug; Zyvox, an antibiotic; and Lyrica, an anti-epileptic drug, causing false claims to be submitted to government health care programs for uses that were not medically accepted indications and therefore not covered by those programs.

The civil settlement also resolves allegations that Pfizer paid kickbacks to health care providers to induce them to prescribe these, as well as other, drugs. The federal share of the civil settlement is $668,514,830 and the state Medicaid share of the civil settlement is $331,485,170. This is the largest civil fraud settlement in history against a pharmaceutical company, the press release said.

Pfizer also has agreed to enter into an expansive corporate integrity agreement with the Office of Inspector General of the Department of Health and Human Services. That agreement provides for procedures and reviews to be put in place to avoid and promptly detect conduct similar to that which gave rise to this matter, the Justice Department said.

According to the Justice Department, the settlement is the result of the investigation instigated by six whistleblowers. As a result of the settlement, the whistleblowers will receive $102 million of the federal fines.

Pfizer to Pay Big Fine Over Bextra Promotion

Thu, 29 Jan 2009 00:00:00 -0800

Drug maker Pfizer, Inc. led the news with two announcements this week: It took a record-breaking hit of $2.3 billion over investigations into its improper marketing of the painkiller Bextra and other medications and it is acquiring its rival, Wyeth, for $68 billion, reported Bloomberg News. Pfizer recalled Bextra in 2005 over a rare skin condition and at the urging of the U.S. Food and Drug Administration (FDA).

Pfizer reached the $2.3 billion agreement with the Massachusetts U.S. Attorney to, it said, “resolve previously disclosed investigations" regarding Bextra and "other open investigations," reported Bloomberg, which added that while Pfizer disclosed no other details, its fourth-quarter earnings dropped a massive 90 percent over the charges and investigation. The Wall Street Journal blog (WSJ) noted that Pfizer’s fourth-quarter earnings dropped to $266 million from $2.72 billion the prior year.

According to Bloomberg News, the Pfizer settlement is the largest for allegations of off-label marketing practices, a topic of concern to consumers, the medical community, and patient advocates. The prior record had occurred earlier this month when Eli Lilly & Company paid out $1.42 billion over its antipsychotic Zyprexa, said Patrick Burns of Washington advocacy group Taxpayers Against Fraud, reported Bloomberg. Pfizer spokesman, Christopher Loder, explained that the $2.3 billion settlement represents an "agreement in principle to resolve government allegations of past off-label practices," said Bloomberg, noting that Loder refused to say what other investigations were covered.

The WSJ noted that Pfizer couched the settlement news around its Wyeth purchase, but noted that Pfizer also agreed to pay $745 million for agreements in principle to settle personal injury suits over painkillers Bextra and Celebrex, late last year. FT.com said that amid news of the Wyeth takeover, a “tiny reference” was made in Pfizer’s fourth-quarter results issued on Monday that mentioned the record-breaking $2.3 billion agreement in principle. Also, said WSJ, there was $60 million for attorneys general in 33 states and the District of Columbia, and $89 million to resolve class actions, which were not included in the “investigation by the Department of Justice of the marketing of the company’s Cox-2 medicines, particularly Bextra,” Pfizer said in a recent quarterly filing, reported the WSJ.

Pfizer has also beeh hit hard by a number of other factors, said the Journal, including competition with the generic version of allergy medication Zyrtec and reports about odd and controversial reactions to Chantix, its smoking cessation medication. Chantix sales dropped by $36 percent—to $180 million—when stories of bizarre reactions to the medication began surfacing and making the news. To make matters worse, said the WSJ, the combined Pfizer-Wyeth will be reducing staff by 10 percent, which is part of a larger 15 percent reduction. The workforce reduction translates into about 19,500 jobs.

Pfizer acquired Bextra in a takeover of Pharmacia, which was finalized in 2000, reported FT.com. Bextra, a Cox-2 painkiller is in the same class as Merck’s Vioxx, which was withdrawn in 2004 following reports that Vioxx was linked to an increased incidence of heart attacks. Meanwhile, Pfizer’s Celebrex, another Cox-2 painkiller, which was associated with skin infections and concerns over cardiac risk pushed the FDA to seek the drug’s withdrawal, said FT.com.

Arizona Bextra Lawsuit Charges Pfizer with Deceptive Marketing

Wed, 19 Nov 2008 00:00:00 -0800

In 2005, the U.S. Food and Drug Administration (FDA) and European regulators formally asked Pfizer, Inc. to suspend sales of Bextra in the United States and Europe. As a result, Pfizer announced it would halt sales of the drug in the United States and the European Union countries immediately. The FDA stated that the risks—a high rate of heart attacks, strokes, other cardiovascular injuries, and Stevens Johnson Syndrome—posed by Bextra outweighed its benefits. Now, the Zonie Report has published a piece discussing yet another lawsuit involving Pfizer, this time over deception in marketing.

Zonie is reporting that the Arizona Attorney General filed a 15-page court complaint that alleges that Pfizer repeatedly conned consumers to increase Bextra sales; the lawsuit states that Pfizer misrepresented Bextra risks, enlisting doctors to promote the drug to increase sales. The FDA approved Bextra for “treatment of arthritis and menstrual pains.” According to Zonie, the lawsuit says that Pfizer: “Withheld studies that showed safety risks, deployed an enormous sales staff to promote Bextra’s “off-label” uses, and gave improper gifts to physicians in return for their help marketing the product.”

Lawyers for the Attorney General claim that the “deceptions began in 2001” following the FDA’s declination of Bextra approval for all of the “off-label” uses for which Pfizer was seeking approval, said Zonie, which added that Pfizer settled with the federal government for nearly $900 million. The state’s suit also alleges that Pfizer was looking to promote Bextra for treatment for “acute and perioperative pain” and also to help with “gastrointestinal side effects,” all without appropriate and complete research.

Zonie notes that the controversy involves COX-2 inhibitors, medications that block pain and inflammation and that the complaint states that three COX-2 inhibitors received FDA approval. Pfizer released Celebrex in early 1999; soon after Merck released Vioxx. In 2004, Merck removed Vioxx—known generically as Rofecoxib—after data from a clinical trial found an increased risk of heart attack and stroke, blood clots, and other cardiovascular complications. The complaint states that, in 2004, Bextra was withdrawn and Celebrex received a “black box” label warning, notes Zonie.

Despite looming lawsuits, Pfizer apparently continued to sell Bextra as a pain killer and—according to the Zonie report regarding the contents of the complaint—minimized the findings of a negative study, bought research from advertising agencies with which it contracted, and arranged for the publication of positive studies publish in a major medical journal before editors were able to retract the piece. Also, according to the Zonie piece, Pfizer also only disclosed “favorable” Bextra data, running ad campaigns promoting Bextra as the “ideal pain-killer” for the “weekend warrior”; and “also sought out and developed physician speakers who were high prescribers of Bextra and supported its off-label use,” according to the complaint. “These health care providers were then paid to give lunch or dinner talks relating to off-label use of Bextra,” Zonie quoted from the complaint.

Zonie noted that the complaint detailed how sales staff would join doctors on their presentations, with the most successful doctors “rewarded with ‘preceptorships’ in which they received up to $500 to allow Bextra sales reps to accompany them on their rounds or in the operating room,” said Zonie. The state Attorney General is seeking a permanent injunction barring Pfizer from continuing these alleged practices in Arizona.

COX-2 Inhibitors More Likely to Raise Heart Risks Than Other NSAIDs

Wed, 05 Nov 2008 00:00:00 -0800

A new study that confirms the heart risks associated with a class of drugs called NSAIDs has found that the increased risk correlates to the specific pain-causing molecule they act against. According to the study, NSAIDS that are cox-2 inhibitors are more likely to increase the risks of heart attacks and strokes.

NSAIDs are the most prescribed medications for treating conditions such as arthritis. Most people are familiar with over-the-counter, nonprescription NSAIDs, such as aspirin and ibuprofen. NSAIDs also include prescription drugs like Celebrex, as well as the now-banned Vioxx.

NSAIDS target different forms of cyclooxygenase, an enzyme whose activity increases inflammation and pain. Older NSAIDs, such as ibuprofen and naproxen, act primarily against cox-1. Celebrex, Vioxx and Bextra act against cox-2. While cox-2 inhibitors reduce the gastrointestinal bleeding, pain and inflammation that are major side effects of the cox-1 drugs, they have been found to increase the risk of heart attack and stroke.

This latest study, conducted by researchers in Spain and Italy, looked at 8,852 people who had heart attacks. The increase was related to both the dosage and the length of time the drugs were taken. But the risk was increased by 18 percent by NSAIDS that acted against cox-1, compared to a 60 percent increase for those with the greatest cox-2 activity.

"We found a significant correlation between the degree of inhibition in vitro [in the laboratory] of whole blood cox-2, but not whole blood cox-1," said the report by researchers in Spain and Italy.

The Food & Drug Administration (FDA) now requires all COX-2 inhibitors and NSAIDs to bear a black box warning regarding heart attack and stroke risks. The warnings were added to the drugs after Vioxx was recalled in 2004.

Vioxx was approved for use in 1999, and quickly became a blockbuster for Merck, with annual sales of $2.5 billion. But the FDA ordered Vioxx off the market in 2004 after studies showed that people who took the drug had a higher risk for heart attack. The recall came after an analysis of patients using Vioxx linked the defective drug to more than 27,000 heart attacks or sudden cardiac deaths in the U.S. from 1999 through 2003. Since then, Vioxx the subject of thousands of drug injury law suits.

Late last year, Merck announced that it would a $4.85 billion settlement with Vioxx plaintiffs. Under the terms of the Vioxx settlement, Merck set up $4 billion fund for people who claim they suffered heart attacks as a result of Vioxx, and another $850 million fund for those who suffered ischemic strokes. Initial payments for the Vioxx settlement started going out to some plaintiffs last month.

Pfizer Announces Bextra, Celebrex Settlement

Fri, 17 Oct 2008 00:00:00 -0700

Pfizer has reached a tentative agreement to settle lawsuits involving its Bextra and Celebrex painkillers for $894 million. If it goes forward, the Pfizer Bextra and Celebrex settlement will resolve roughly 90 percent of the personal injury lawsuits the company faces because of the drugs.

Celebrex and Bextra are COX-2 inhibitors, a class of drugs that also includes Merck’s recalled Vioxx. Such medications are linked to an increased risk of blood clots, heart attacks and strokes. Pfizer withdrew Bextra from the market in 2005, and Celebrex is the only COX-2 inhibitor still on the market in the United States.

Celebrex carries the Food and Drug Administration’s (FDA) strictest “black-box” warning on its drug label, stating that it may cause an increased risk of serious cardiovascular events such as heart attacks and strokes. Despite its apparent risk, Celebrex continued to generate $2.3 billion in sales in 2007, a 12 percent increase from the previous year.

According to The New York Times, $760 million of the Bextra and Celebrex settlement would go to settle roughly 7,000 personal injury cases, $60 million will cover settlements with attorneys general in the 33 states and the District of Columbia, and $89 million will cover consumer fraud class action cases over reimbursement for money spent on the two drugs.

Pfizer said it hopes to finalize the settlement by the end of the year. A spokesperson for the company said that Pfizer would also like to include many of the remaining personal injury lawsuits the settlement. The company will fight those not settled with court motions or at trial.

COX-2 inhibitors have been the subject of safety worries since 2004, when Merck pulled Vioxx from the market. The FDA ordered the painkiller off the market after an analysis of patients using Vioxx linked the defective drug to more than 27,000 heart attacks or sudden cardiac deaths in the U.S. from 1999 through 2003. The Vioxx recall led to thousands of lawsuits.

Last November, Merck announced a $4.85 billion settlement with the thousands of people who had filed Vioxx injury lawsuits. Under the terms of the settlement, Merck set up a $4 billion fund for people who claim they suffered heart attacks as a result of Vioxx, and another $850 million fund for those who suffered ischemic strokes. Partial settlement payments started going out to some Vioxx plaintiffs last month.

Study Confirms Vioxx and Bextra Dangers

Fri, 08 Aug 2008 00:00:00 -0700

Another study has confirmed that Vioxx and Bextra increase the risk of having a stroke. Both Bextra and Vioxx were removed from the market because of their association with heart attacks and stroke.

This latest study, which looked at the stroke risk of COX2 inhibitors like Vioxx and Bextra, as well as the risk of other NSAIDs like ibuprofen, was conducted by researchers at Vanderbilt University in Tennessee. The study focused on the seven most common NSAIDs, including Celebrex, Vioxx, Bextra, ibuprofen, naproxen, indomethacin, and diclofenac.

Among the participants, 78,036 were current users of one of the seven study NSAIDs, 16,420 were current users of other NSAIDs or NSAID combinations, and 242,450 were nonusers.

The study found that the risk of stroke was 28 percent higher among Vioxx users and 41 percent higher among Bextra users. The risk of stroke was not significantly increased with Celebrex or with other NSAIDs

In an interview with Reuters news service, lead researcher Dr. Christianne Roumie said the decisions to take Vioxx and Bextra off the market were justified. "This study suggests that rofecoxib (Vioxx) and valdecoxib (Bextra) were associated with higher stoke risk than other NSAIDs," Roumie said in the interview.

"Because of this and other studies, their withdrawal from the market is appropriate and these medications should not be re-introduced, especially since safer alternatives are available," she explained.

Bextra, made by Pfizer, was removed from the market in 2005. In May, The Wall Street Journal reported that Pfizer had reached settlements with three law firms representing patients who sued over the drug. Pfizer was reportedly offering such patients as much as $200,000 to settle their Bextra cases.

Vioxx was recalled in 2004. Last November, Merck announced a $4.85 billion settlement with the thousands of people who had filed Vioxx injury lawsuits. Under the terms of the settlement, Merck set up a $4 billion fund for people who claim they suffered heart attacks as a result of Vioxx, and another $850 million fund for those who suffered ischemic strokes. Partial settlement payments are expected to start going out this month.

Pfizer Negotiating Celebrex, Bextra Settlements

Mon, 05 May 2008 00:00:00 -0700

Celebrex and Bextra maker Pfizer Inc. has begun to settle injury claims against the painkillers. It is estimated that between 7,000 and 9,000 Celebrex and Bextra cases have been filed by people who claim the defective painkillers caused heart attacks and strokes. According to a report in Friday's Wall Street Journal, lawyers representing Pfizer have indicated the company is willing to pay as much as $500 million to resolve all outstanding cases.

Celebrex and Bextra are COX-2 inhibitors, a class of drugs that also includes Merck's recalled Vioxx. Such medications are linked to an increased risk of blood clots, heart attacks and strokes. Pfizer withdrew Bextra from the market in 2005, and Celebrex is the only COX-2 inhibitor still on the market in the United States.

According to The Wall Street Journal, Pfizer has reached settlements with three law firms representing more than 200 of the thousands who sued over the drugs. Firms have been offered $40,000 to $50,000 a client to resolve Celebrex cases and as much as $200,000 a client for Bextra. The Wall Street Journal reported that unlike Merck's recent mass settlement of litigation involving Vioxx, Pfizer is attempting to resolve its Bextra and Celebrex lawsuits on a firm-by-firm basis.

Celebrex carries the Food and Drug Administration’s strictest “black-box” warning on its drug label, stating that it may cause an increased risk of serious cardiovascular events such as heart attacks and strokes. Despite its apparent risk, Celebrex continued to generate $2.3 billion in sales in 2007, a 12 percent increase from the previous year.

Last month, the National Cancer Institute released an analysis of six Celebrex studies that included 7,950 patients. According to The Wall Street Journal, the analysis showed Celebrex was associated with an increased risk of cardiovascular death, heart attack, stroke, heart failure or thromboembolic event, or events related to blood clots, compared to patients not taking the drug. The researchers found that patients receiving the highest dose of Celebrex of 400 milligrams twice daily had a nearly three times higher risk of heart attacks and strokes than patients not taking the drug. Patients taking a lower dose of Celebrex, 400 milligrams once daily, had a 10% higher risk of a cardiovascular event. The study did not look at patients taking a once-daily, 200-milligram dose of Celebrex, which represents the way the drug is most commonly prescribed.

The first Bextra trial was due to begin today in federal court in San Francisco. But a lawyer involved in the case told The Wall Street Journal that the parties agreed to adjourn the case so Pfizer could attempt to settle Celebrex and Bextra cases across the country.

Ex Pfizer Sales Manager Indicted For Allegedly Obstructing Off-label Marketing Probe

Fri, 14 Mar 2008 00:00:00 -0700

An investigation of Pfizer Inc. drug marketing efforts has resulted in charges being filed against a former Pfizer sales manager. The four count indictment alleges that the former Pfizer employee tried to obstruct an investigation into possible off-label marketing of some Pfizer medications.

The four-count indictment issued by the U.S. District Court in Massachusetts stemmed from an investigation into charges that Pfizer was marketing two drugs for unapproved uses. Though doctors are allowed to prescribe approved drugs any way they see fit, drug companies are barred from promoting such off-label uses.

Though the indictment does not name which Pfizer drugs were the subject of the investigation, the Pharmalot Website is reporting they were Bextra and Celebrex.

Celebrex and Bextra are COX-2 inhibitors, a class of drugs linked to an increased risk of blood clots, heart attacks and strokes. Pfizer withdrew Bextra from the market in 2005, and Celebrex is the only COX-2 inhibitor still on the market in the United States.

Thomas Farina, 41, of Fairport, N.Y., supervised about 10 Pfizer sales representatives in the Brooklyn, N.Y., area. According to the indictment, Farina is accused of altering and deleting computer files, as well as instructing employees he supervised to do the same, despite knowing that Pfizer was under investigation for promoting two drugs for unapproved uses. The indictment said Farina had been given specific instructions to preserve all documents related to the investigation.

The indictment alleges that Farina changed the clock on his computer and then altered and re-saved files to make them appear to have been changed at an earlier time. Many of the files, which involved instructions to promote drugs at unapproved dosages or for unapproved uses, were then deleted, according to the indictment.

The indictment also alleges that Farina told others to alter and delete documents related to the investigation of off-label drug promotions. The investigation found that Farina had known that Pfizer was being probed for off-label marketing at the time he deleted the files.

If convicted, Farina would face up to 20 years in jail and a $250,000 fine on each of the four counts against him.

Painkillers, cholesterol linked

Tue, 13 Feb 2007 00:00:00 -0800

Certain pain-relieving drugs that belong to a group of medications called COX inhibitors may impair the ability of human blood cells to rid themselves of cholesterol, according to research published Jan. 23 in the journal Arthritis Research & Therapy.

The finding suggests an explanation for an increased risk of heart attacks in people who used Vioxx and Bextra called COX-2 inhibitors and could help the pharmaceutical industry develop new arthritis pain drugs.

The researchers, including two at Winthrop-University Hospital in Mineola, wanted to determine whether something other than blood clots contributed to heart problems linked to Vioxx.

Dr. Allison Reiss, head of the inflammation section of Winthrop's Vascular Biology Institute, was the lead researcher. Dr. Steven Carsons, chief of Winthrop's Division of Rheumatology, Allergy and Immunology, also participated.

The study found excess cholesterol and blood clots together may have caused side effects linked to Vioxx and Bextra.

Vioxx and Bextra were taken off the market in 2004 and 2005, respectively. Vioxx showed a higher risk of heart attack and stroke in people using it longer than 18 months. Bextra sparked concerns about life-threatening skin reactions and cardiovascular problems.

The researchers found chemical equivalents of certain COX inhibitors diminished naturally occurring prostaglandins and caused lipid buildup in human blood cells that they studied in culture. "The remarkable thing was that the drugs all compromised the mechanism that rids cells of cholesterol," Reiss said.

Adding back prostaglandins helped restore the cholesterol balance.

Pfizer Inc., which sold Bextra, issued a statement: "This study represents an interesting new theory about why all NSAIDS [non-steroidal anti-inflammatory medicines], including selective and non-selective, may impact heart health." Pfizer said further work is needed.

A statement from Merck and Co. Inc., which made Vioxx, said: "At this time, Merck has not yet had the opportunity to examine the paper's methodology or the authors' conclusions with the rigor appropriate for the review of any scientific study, particularly one which seeks to draw conclusions about human health from experiments performed in a laboratory rather than from clinical trials in humans."

Study Links Certain Painkillers to High Cholesterol Levels

Tue, 13 Feb 2007 00:00:00 -0800

A new study published last month in the journal Arthritis Research & Therapy sheds new light on why the class of painkillers known as COX-2 inhibitors may lead to an increased incidence of heart attacks. Researchers at Winthrop-University Hospital in Long Island have determined that controversial drugs such as Vioxx and Bextra may impede the body’s ability to purge excess cholesterol.

“To our knowledge, this is the first study that describes the effects of COX inhibition on reverse cholesterol transport proteins,” the authors wrote. “Our results suggest that the cardiovascular hazard observed with COX inhibitors may result not only from enhanced platelet aggregation [blood clots], but also from interference with cholesterol outflow.”

Drugs such as Vioxx and Bextra were commonly prescribed in the treatment of arthritis pain before they were each removed from the market by the FDA due to safety concerns. The new research suggests that these medications block the patient’s ability to process lipid loads, allowing cholesterol to build up. To this point, researchers have focused on the risk of blood clotting as the leading cause of cardiovascular problems in these patients. “Increased cardiovascular risk with COX inhibition may be ascribed at least in part to altered cholesterol metabolism,” they claim.

“Selective COX-2 inhibitors reduce pain, stiffness, and inflammation with efficacy equivalent to non-selective NSAIDs, but with reduced gastrotoxicity,” the researchers note. “Unfortunately, adverse effects on coronary heart disease risk with prolonged use of COX-2s may offset any gastrointestinal benefit.”

Merck's Worst Nightmare, a Study that Shows Vioxx Heart Attack Risk Linked to (Very) Short-Term Use

Wed, 03 May 2006 00:00:00 -0700

Throughout the Vioxx saga, Merck has always taken refuge behind its assertion that short-term use of the COX-2 inhibitor cannot be linked to an increased risk of heart attack or stroke. Merck itself, however, acknowledges long-term use of the drug does carry such an increased risk. In fact, the long-term adverse implications of Vioxx use led to the voluntary withdrawal of the drug in September, 2004.

To a great extent, Merck has legitimized its strategy of refusing to settle any of the roughly 12,000 Vioxx personal injury and wrongful death cases on the basis of its conviction that it should ultimately prevail on all of the short-term cases (by dismissal, verdict, or on appeal) thereby eliminating about half of the cases.

Merck also believes that even many of the long-term-use Vioxx plaintiffs suffered their injuries (or deaths) as a result of one or more chronic medical condition such as cardiovascular disease, diabetes, hypertension, or obesity.

Thus, the pharmaceutical giant sees no reason to enter into a global settlement of all pending lawsuits against it as long as the company and its attorneys still perceive so many “defensible” cases exist.

Unfortunately for Merck, however, things have not turned out that way since it has already lost three lawsuits, including two short-term-use cases, and has been found liable for punitive damages, which are not covered by insurance, in each of those cases. Nonetheless, the lack of definitive proof linking short-term use of Vioxx to an increased risk of heart attack and stroke has kept Merck on the offensive and putting plaintiffs to their proof.

Now, however, that confidence has to have been shaken by the results of a Canadian study published in the Canadian Medical Association Journal. That study analyzed data on 114,000 patients and reported that 239 people in Quebec, 66 and over, suffered heart attacks while taking Vioxx between 1999 and 2002.

None of the Vioxx users had a history of heart attack. The Celebrex users did not exhibit any such statistical increase in heart attack risk.

An analysis of the data indicates that over 25% of those people had their heart attacks within two weeks of their first prescription for Vioxx. The team found that “among elderly users of predominantly low doses of these agents, short-term use of rofecoxib is not without risk, and that risk of MI [heart attack] is not restricted to continuous users nor accentuated with longer-term use."

Thus, the researchers see the need for early monitoring of COX-2 side-effects as well as continued monitoring of patients after the discontinuance of the medication. Some 30,200 Vioxx and 45,000 Celebrex users were studied for about 2 ½ years.

Of the 239 heart attacks in Vioxx patients, 65 took place within only 9 days of starting Vioxx therapy.

Plaintiffs’ attorneys see the Canadian study as a major setback for Merck’s defense strategy that will make even the shortest-use cases more viable and far less defensible. It could also prompt Merck to reconsider its position on settlement.

Study Finds Vioxx Dangers Occur Earlier Than Expected

Wed, 03 May 2006 00:00:00 -0700

Researchers report that heart risks from the withdrawn painkiller Vioxx occur much earlier than had been expectec. Twenty-five percent of heart attacks occurred within the first two weeks of use, a new study found.

A new study led by Queen's University researcher Linda Lévesque shows that heart attacks related to the use of Vioxx a drug once popular for the treatment of pain and inflammation can occur within the first two weeks of use.

A quarter of patients who suffered a heart attack while taking Vioxx did so within the first two weeks of their first Vioxx prescription, said Lévesque, of Queen's Department of Community Health and Epidemiology.

"This demonstrates that cardiovascular risks from taking Vioxx may occur much earlier than previously believed," she said. Conducted with McGill University researchers James Brophy and Bin Zhang, the findings appear on-line in the Canadian Medical Association Journal.

"Our previous study on COX-2 inhibitors, which included Vioxx and Celebrex, evaluated whether there was an increased risk of heart attack while taking these medications; the answer was yes for Vioxx," explained Lévesque.

In the current study, funded by the Canadian Institutes for Health Research (CIHR), the pattern of cardiovascular risk in Québec seniors was assessed over a three-year period.

The additional cardiovascular risk actually decreased with longer duration of use, suggesting that the period of highest susceptibility for most people taking Vioxx may occur earlier than previously believed. The study also documents that cardiovascular risk returns to normal within one month of stopping the drug.

Vioxx was voluntarily withdrawn from the market on September 30, 2004, after a study showed that it doubled patients' risk of heart attacks and strokes after 18 months of use.

This study is the first to specifically address the question of the timing of cardiovascular risk associated with COX-2 inhibitors.

Painkiller may double risk of heart attacks

Wed, 01 Mar 2006 00:00:00 -0800

A drug used to treat thousands of patients in Britain for chronic pain in conditions such as arthritis has been linked with a doubling of the risk of heart attacks, according to a new study. The drug, Celebrex, is the third drug of its type to raise safety concerns.

Vioxx was withdrawn by its makers two years ago because of cardiovascular complications and Bextra was withdrawn last year because of skin reactions.

In 2004 about 2.5 million people were using Celebrex, but the numbers are known to have reduced substantially since concerns about the drugs were raised.

In the latest study, when researchers pooled the evidence from four existing studies which compared Celebrex with a placebo, they found that it was associated with a 2.26-fold increase in heart attacks.

The studies involved 4,422 patients who had taken the drug for at least six weeks.

A second analysis of 12,780 patients in six other studies suggested the drug gave a 1.88-fold increased risk of heart attack when compared with other pain killers including ibuprofen, paracetamol and diclofenac.

Celebrex, or celecoxib, is one of a class of drugs called Cox-2 inhibitors which were hailed as a breakthrough in the treatment of severe pain.

Traditional treatments like aspirin and ibuprofen are linked to stomach bleeding but the Cox-2s avoided this potentially serious side effect. Celebrex continues to be licensed for pain but doctors are advised to use the lowest effective dose, to avoid long term treatments and not to prescribe it for patients at risk of cardiovascular disease.

Some laboratory research has suggested that Cox-2s may create an imbalance that favours blood clotting and narrowing of blood vessels.

The latest study, in the Journal of the Royal Society of Medicine, adds to the debate over the safety of Cox-2s.

Prof Richard Beasley, of the Medical Research Institute of New Zealand, said yesterday: "Our evidence shows an increased risk of heart attack in patients taking celecoxib.

"Drug regulatory authorities urgently need to re-examine the assessment of the drug in light of these findings."

A spokesman for the manufacturers, Pfizer, said the study sample was small and that the regulatory authorities had carried out extensive studies on Celebrex of their own.

"They were looking at a relatively small sub-set of data. We would point to the combined analysis by regulatory authorities that looked at 40,000 patients.

"This showed a risk similar to older therapies like ibuprofen.

''The other point was that the dose given was above the recommended dose for the majority of cases."

The spokesman said many patients had been given an 800mg dose when the licensed dose is 200mg to 400mg daily.

Pfizer is starting a new long term trial of Celebrex.

Analysis: Celebrex ups heart-attack risk

Tue, 28 Feb 2006 00:00:00 -0800

A meta-analysis released Tuesday indicates Pfizer's Celebrex increases the risk of a heart attack by over two-fold and experts are calling for regulatory authorities to respond promptly to the new findings.

"It's an important finding that regulators need to consider in future prescriptions of this drug," Kamran Abbasi, editor of Journal of the Royal Society of Medicine, where the study was published, told United Press International.

Asked if he thought Celebrex should be taken off the market, Abbasi said, "I'm not saying that." But he added, "This is new data suggesting the risk profile of myocardial infarction is somewhat similar to the risk profile of Vioxx and we know what happened with that, so we need to be careful with this drug."

Merck withdrew Vioxx from the market in 2004 after it was linked to an increased risk of heart attacks and strokes.

Richard Beasley, the principal author of the study and a professor at New Zealand's Medical Research Institute, also thought regulatory officials should take a closer look at Celebrex.

"Our evidence shows an increased risk of heart attack in patients taking celecoxib," Beasley said. "Drug regulatory authorities need to urgently re-examine the assessment of the drug in light of these findings."

Beasley noted the myocardial infarction risk with Celebrex seen in his meta-analyses is similar to a 2.24-fold increased risk with Vioxx that was reported in a separate meta-analysis.

"It will be interesting to see if the drug regulators tighten restrictions and whether celecoxib is now withdrawn as occurred with Vioxx," he added.

However, some experts think the findings are consistent with what was already known about COX-2 inhibitors.

"I don't think this is a huge increment in our knowledge but it does continue to support the notion that there is some potential concern with COX-2 inhibitors and cardiovascular events," David Harrington, a professor in the section on cardiology at Wake Forest University School of Medicine, told UPI.

"At this point, I don't see this as sufficient grounds to change what we previously recommended about COX-2 inhibitors," added Harrington, who also serves as a spokesman for the American Heart Association.

Pfizer criticized the meta-analysis design of the study and pointed out that previous studies had not found an increased risk of heart attacks in Celebrex patients.

"It's not a well-designed study," Pfizer spokeswoman Cathy Cantone told UPI. She also noted that Celebrex had been studied in more than 40 randomized, controlled trials involving nearly 45,000 patients. Of the nearly 25,000 people who took Celebrex, the drug was not associated with an increased risk of heart stroke or cardiovascular deaths when compared with those who received nonspecific NSAIDs.

In the study, Beasley's team conducted two meta-analyses of 10 studies involving Celebrex. In the primary meta-analysis, four trials with more than 4,400 patients were reviewed and the researchers found a 2.26-fold increase in myocardial infarction in patients treated with Celebrex compared to those on placebo. There was no significant increase in risk in composite cardiovascular events, cardiovascular deaths or stroke in the Celebrex patients.

The secondary meta-analysis included six studies involving a total of 12,780 patients treated with placebo, diclofenac, ibuprofen, paracetamol or Celebrex. The Celebrex patients had a 1.88-fold increased risk of myocardial infarction.

The study comes on the heels of a Pfizer-funded study released last week that found no increased risk of cardiovascular or cerebrovascular problems in Celebrex patients compared to those who received naproxen or diclofenac.

However, that study, which is called SUCCESS-I and appeared in the March issue of the American Journal of Medicine, was not designed to look at those issues and Pfizer backed away from giving Celebrex the all clear. Instead, the company said it was waiting on the results of the PRECISION trial, which is slated to begin later this year.

There are other COX-2's in the pipeline, including one GlaxoSmithKline is developing and Novartis' Prexige, that could offer some competition in the coming years, but some analysts think Celebrex will likely retain the predominant share of the market if it is not withdrawn.

Trial Date for Celebrex Suit Set for June

Mon, 27 Feb 2006 00:00:00 -0800

A judge set a June 6 trial date for a lawsuit filed by a woman who claims the arthritis medication Celebrex was to blame for a stroke she suffered last year.

Barring delays, plaintiff's attorneys said Monday the trial could be the nation's first over the popular pain medicine by Pfizer Inc., which projected more than $2 billion in sales for Celebrex this year.

Rosie Ware contends Celebrex was to blame for a stroke she suffered a year ago at age 53. She claims Pfizer and companies it has since purchased understated the risks of the drug and failed to warn consumers of possible side effects.

An attorney for Ware, said about 450 lawsuits have been filed over Celebrex.

A Pfizer spokesman did not immediately return a phone call seeking comment. The drug's Web site includes a warning that Celebrex may increase the risk of stroke or heart attack in some people.

Celebrex is part of a class of drugs called cox-2 inhibitors. It is the only one of its type remaining on the market after Merck & Co.'s Vioxx and Pfizer's Bextra were withdrawn because of safety concerns.

Merck withdrew Vioxx in September 2004 after a study showed it doubled patients' risk of heart attacks and strokes after 18 months of use. The company now faces more than 9,600 lawsuits over Vioxx.

Pfizer is funding a study to determine whether Celebrex leads to more heart problems than other pain relievers.

Strange Goings On at the Cleveland Clinic: Mere Coincidences or Something Far More Problematic?

Mon, 19 Dec 2005 00:00:00 -0800

If you like playing the game “connect the dots,” you might find this one very interesting:

2001 – Drs. Eric Topol and his associate (and subordinate) at the prestigious Cleveland Clinic, Steven Nissen, jointly attack COX-2 inhibitors and especially Vioxx The concerns arising out of the VIGOR study were crystallized by Topol, Nissen, and Debabrata Mukherjee in JAMA in their review paper specifically highlighting the cardiovascular side-effect profile of COX-2 inhibitors. On August 22, 2001 a study published in Journal of the American Medical Association by Drs. Topol, Nissen, and Mukherjee indicated that Vioxx was linked to a 200% increase in blood clots, heart attacks, and strokes based on their review of previous clinical trials.

2004 – Vioxx is pulled from the market and Dr. Topol goes on a relentless attack along the lines of “I told you so” in articles and comments such as the one to the Washington Post (10/1/04) where he stated that Merck’s action was “the right decision about three years too late. This is the sort of thing that Merck should have studied earlier, but they were too busy refuting the warning signs.”

2005 – Vioxx court trials begin and Dr. Topol remains adamant about the cardiovascular risks posed by Vioxx. He is the vocal face of the Cleveland Clinic in the COX-2 saga and certainly the last person in the world Merck or Pfizer would ever want to rely on as a last hope to salvage the multi-billion dollar market for Vioxx or Celebrex.

2004-2005 – Dr. Nissen remains uncharacteristically silent especially in light of his long-standing criticism of the COX-2 inhibitors and Vioxx.

November 2005 – Under subpoena in the first federal Vioxx trial, Dr. Topol pulls out all the stops and offers a three-hour videotaped deposition (much of which was shown to the jury) attacking Vioxx as a dangerous drug from a cardiovascular standpoint and accuses Merck of engaging in scientific misconduct, suppressing clinical evidence and stifling medical discourse as it promoted the painkiller. He also calls certain aspects of Merck's behavior "repulsive" and "appalling." The deposition is shown to the jury on Saturday, December 3, 2005.

December 8, 2005 – Less than a week after his devastating anti-Vioxx, anti-Merck testimony is shown to the jury (and in the midst of the NEJM accusation that Merck manipulated the outcome of the VIGOR study by deleting data relating to at least three heart attack-related deaths) the Cleveland Clinic suddenly announces that Dr. Topol has been stripped of his prestigious position as chief academic officer of the Clinic's medical college. This significant demotion at a time when the Clinic was thrust into the public eye by Dr. Topol’s highly consumer-friendly testimony is described as nothing more than part of a broader administrative reorganization making his “position was no longer needed.”

December 9, 2005 – Dr. Topol states: “The hardest thing in the world is just telling the truth, to do the right thing for patients, and you get vilified. No wonder nobody stands up to the industry.”

December 13, 2005 – Pfizer announces a $100 million study will be launched into the safety of its own drug, Celebrex. Amazingly (or maybe not so amazingly at that) the Cleveland Clinic is to conduct the study and leading the research will be none other than Dr. Nissen himself.

With Celebrex as the only COX-2 inhibitor remaining on the U.S. market, the multi-billion dollar blockbuster will either have the field to itself or be declared no worse than its sister-drugs Vioxx and Bextra. (Prior studies have already indicated that Celebrex was probably the least risky of the COX-2s from a cardiovascular risk profile.)

The $100 million study is little more than a prudent investment by Pfizer. It makes the world’s biggest pharmaceutical company look good from a consumer standpoint. The outcome is thus, anticlimactic. COX-2s will either be shown to be dangerous as a class, which is what most experts already think now, or Celebrex will be vindicated as the safest of the three drugs and remain the only COX-2 on the market.

And, all of this (and $100 million of Pfizer’s money) is being placed in the hands of the Cleveland Clinic and Dr. Nissen.

Dr. Eric Topol has been Provost, Cleveland Clinic Lerner College of Medicine, Chief Academic Officer and Chairman, Department of Cardiovascular Medicine, and Professor of Medicine and Genetics, Case Western Reserve University. He was appointed to the Cleveland Clinic in 1991 after a f ellowship at Johns Hopkins Hospital, an internship at University of California-San Francisco School of Medicine, and a residency at University of California-San Francisco School of Medicine. He attended University of Rochester School of Medicine and Dentistry in Rochester , New York . He is a specialist in interventional cardiology, thrombolytic agents, arterial biology research, and restenosis.

Dr. Steven Nissen currently has no supervisory position or department level chairmanship at the Cleveland Clinic. His appointment to the Clinic was in 1992 after a fellowship at the University of Kentucky Chandler Medical Center, an internship at University of California Davis Medical Center, and a residency at the University of California Davis Medical Center. He attended the University of Michigan Medical School. His specialties include intravascular ultrasound, digital angiography and computer image processing, and coronary intensive care.

It seems quite odd to many observers that the doctor with the superior qualifications would have his leadership position done away with as part of an administrative reorganization making that position “no longer needed” at a time when he would be the ideal person to lead the independent study of Celebrex.

Dr. Topol, however, is hardly the type of professional who could be expected to play a subservient or submissive role and that could have made his participation in the study problematic for his superiors who did not need added attention at a time when the Clinic’s independence and credibility are being questioned.

The prestigious Cleveland Clinic Foundation is a prominent medical center regarded as one of the nation's best. Over the years, however, The Clinic’s need to cultivate a workable relationship with the pharmaceutical companies and medical device manufacturers that fund independent studies and other programs became more and more at odds with Dr. Topol’s consumer-oriented image as a crusader against potentially dangerous drugs and their manufacturers.

Dr. Topol’s recent criticisms extended to drugs other than Vioxx. His candor, however, while admired by his supporters is viewed as quite unscientific to his targets and his detractors. His demotion also came at a time when his ongoing dispute with Dr. Delos Cosgrove had become a distraction at the Clinic.

Dr. Cosgove is Chief Executive Officer, Chairman of the Board of Governors, CCF. His appointment to the Cleveland Clinic came in 1975 following an internship at the University of Rochester-Strong Memorial Hospital and residencies at Children's Hospital of Boston, Massachusetts General Hospital, and University of Rochester-Strong Memorial Hospital. He attended University of Virginia School of Medicine Charlottesville and specializes in the surgical treatment of thoracic and cardiovascular diseases, mitral and aortic valve repair, minimally invasive valve surgery, thoracic aneurysms, homografts, use of alternative conduits in coronary artery surgery, and blood conservation.

Dr. Topol has, for now, retained the position of chairman of cardiovascular medicine at the Clinic, but his demotion has drawn attention to the mounting tensions between the Clinic's research mission and its deep ties to the businesses that finance that research. This rift may lead to Dr. Topol’s eventual departure from the Clinic.
The unrest at the Cleveland Clinic is far more than simply a power struggle between Drs. Topol and Cosgrove, however. It is symptomatic of the continued controversy created by the many longstanding corporate ties at the clinic. Those business links involve staff doctors, researchers, Dr. Cosgrove, and the Clinic's board.
The potential for conflicts of interest at the Clinic is illustrative of the way pharmaceutical and medical device companies and the investment community work closely with medical researchers and doctors to develop and promote new medicines and technologies.

Such relationships raise concerns about potential conflicts of interest that could unduly influence medical decisions as to treatment selections or even bias the results of medical research itself.
The pharmaceutical and medical device industries often find themselves in conflict of interest situations when dealing with “independent” research facilities, the FDA, and when releasing critical data and information about specific drug trials, adverse reactions, defects, and malfunctions.

These industries are bound by federal law and ethical standards to be forthcoming and honest about all relevant details concerning their products, even if unfavorable. Yet, exhibiting remarkably human-like behavior, they often withhold, misrepresent, delay, and otherwise improperly manipulate negative information in order to minimize or avoid harmful financial and legal consequences.

The recent revelations concerning Merck’s alleged manipulation of the VIGOR study by deleting critical data concerning cardiovascular-related deaths are but a window into a world few people are aware even exists.
That world, however, is replete with situations where pharmaceutical companies have: (a) ghostwritten medical journal articles relating to drug safety and trials; (b) delayed the completion of market studies and the subsequent release of the data related thereto; (c) prevented full disclosure about drug trials; (d) withheld important data from the FDA and the public; (e) engaged in misleading, improper, and false advertising campaigns; and (f) pressured the FDA and research facilities to take retaliatory actions against employees who expressed opinions detrimental to a drug or device under review or study.

Fast-track approvals, which are usually based on short-term testing of small test groups, have had disastrous results when used for drugs which are specifically designed for long-term or lifetime use by large segments of the population.

Medical device manufacturers are no more credible or trustworthy than their drug manufacturing counterparts and have been caught engaging in similar bad acts.

Some of the more egregious recent examples of this type of objectionable behavior include a study published in the Journal of the American Medical Association (JAMA) in 2004 that found 65% of findings of harmful effects were not fully reported in medical-journal articles. Results are often “cherry-picked” so that only the positive data is published.

The JAMA study also found that 62% of trials had at least one piece of data or one result that was changed, added, or omitted to make the drug appear better.

Recently, Eli Lilly came under scrutiny for suppressing reports relating to the potential increased risk of suicide risk suspected during early clinical trials. Current clinical trial data that has confirmed this elevated suicide risk.
One trial showed that 3.7% of Prozac users attempted suicide while less than 1% of participants on non-SSRI depressants exhibited the same behavior. Thus, it is reasonable to assume that had there been full disclosure of the early trial data and reports, lives could have been saved.

Johnson and Johnson’s heartburn drug Propulsid has been linked to 80 heart-related deaths and 341 injuries. Despite the adverse effects associated with the drug, Johnson and Johnson did not conduct safety studies and pushed to keep Propulsid on the market. Even with strong black-box warnings on the drugs label, Propulsid was prescribed inappropriately to both adults and children.

After five years of reported problems, Propulsid was pulled from the market in 2000. In 2004, Johnson and Johnson agreed to pay up to $90 million to settle pending claims relating to deaths and injuries from Propulsid.
In the past few years, the FDA has issued dozens of warning letters to pharmaceutical manufacturers. The FDA Division of Drug Marketing, Advertising and Communications has about three dozen employees to review 30,000 to 40,000 Direct-to-Consumer (DTC) ads each year. Lester M. Crawford, then Acting Commissioner of the agency noted that “our patience is sometimes worn thin” by all the advertising claims.

In another shocking disclosure, Adrienne Fugh-Berman, a professor of alternative medicine at Georgetown University, claimed that she was asked to write an article for AstraZeneca about the adverse interactions associated with the combination of Coumadin, a blood-thinner, and dietary supplements and medicinal herbs. AstraZeneca hoped that this information about Coumadin would help them begin to market their own experimental blood-thinner, Exanta.

Fugh-Berman claimed that AstraZeneca then sent her the completed article with her name already on it, before she agreed to write anything. AstraZeneca denied the charge. Later on, Fugh-Berman was asked to review a paper for a medical journal which turned out to be the same paper she was previously asked to pass off as her own.

When the FDA established an accelerated-approval program for new drugs in 1992 it required pharmaceutical companies to continue studying and monitoring a drug even after its market approval. Yet a review by Rep. Edward J. Markey, (D., Mass.) showed that pharmaceutical companies have not completed about half of these studies.
The Markey report indicated that out of 91 studies on 42 different products that were approved from 1993 to October 2004, 46 were completed, 42 were not completed, and three were delayed. Markey argued that “it is outrageous that drug companies and the FDA have been dragging their feet when it comes to conducting required post-marketing studies.” Markey plans to introduce a bill that would allow the FDA to state in a label whether or not a drug has received this accelerated approval so that the public is aware that the drug is still undergoing additional studies.

Significantly, the FDA has funded the fast-track approval program with hundreds of millions of dollars in order to ensure that potential blockbuster moneymaking drugs get to market on an accelerated basis. Thus, FDA has placed itself in a compromising position by accepting these huge sums of money from the pharmaceutical industry to fund the agency’s Office of New Drugs which is now expected to “fast-track” drugs to market.

That division has about 740 employees. Unfortunately, no such funding is given to the FDA for post-approval monitoring of adverse reactions and side-effects by the Office of Drug Safety which only has about 112 employees.
On May 19, Able Laboratories stopped all shipments of its products. Four days later Able recalled its entire product line, suspended all manufacturing and withdrew seven approved applications to market various medications. The massive recall was based on what the FDA itself stated were “serious concerns that they (all of Able’s products) were not produced according to quality assurance standards.”

The FDA eventually revealed that its drastic enforcement action was the result of agency inspectors having found massive record falsification and mismanagement by Able in order to elude FDA detection of several defective medications.

Some of the violations included alteration and falsification of test data and covering up deficiencies by changing results. Able has been effectively put out of the pharmaceutical business as a result of its highly improper conduct.
On July 13, the FDA issued and extensive warning to Hitachi Medical Systems America, Inc. for serious reporting violations and problems with respect to its MRI and PET equipment. The warning followed inspections of Hitachi’s medical device manufacturing facilities by an FDA investigator with respect to the magnetic resonance imaging (MRI) systems manufactured by Hitachi Medical, Tokyo, Japan which are medical devices as defined in section 201(h) of the Federal Food, Drug and Cosmetic Act (the Act).

The above inspection revealed that Hitachi’s devices are misbranded in that the company failed to furnish material or information required under the Act and the Medical Device Reporting (MDR) Regulation. Specifically, Hitachi had received complaints relating to four separate events for which it failed to submit an MDR to the FDA within 30 days of receiving information that the devices may have caused or contributed to a death or serious injury.

On May 24, Guidant Corporation disclosed for the first time that it had waited three years before disclosing it had been aware of the electrical problem that had caused some 28 of these defibrillators to malfunction. The revelation came in the form of an alert to physicians which was not issued until Guidant learned that The New York Times was about to publish a story on the defibrillator. There is no doubt among experts that the delay probably caused unnecessary deaths.

When the FDA held hearings in February of this year supposedly to determine if the COX-2 inhibitors were safe enough to remain on the market, more signs of a system with widespread conflicts of interest became disturbingly clear.

Of the 32 government drug advisers who would vote on the issue, 10 had consulted for Merck (Vioxx) or Pfizer (Celebrex and Bextra) in recent years.

When the votes were tallied, the results were shocking to many but not to those who decry the cozy relationship between “independent” researchers, the FDA, and the industries that are supposed to be under scrutiny.
While the committee voted unanimously that all of the drugs significantly increased the risk of heart attack and stroke, Vioxx, a drug pulled from the market by its own manufacturer (Merck) only 3 months before miraculously rose from the ashes on the wings of a 17-15 vote. (Without 9 of the 10 “questionable” votes going in favor of the drug, however, the committee would have voted 14-8 to ban Vioxx).

Bextra, a drug which had even more serious risks associated with it than Vioxx, survived by a margin of 17-13-2 (abstentions). (That vote would have been 12-8 against Bextra without 9 favorable votes from the 10 advisers in question). Bextra was pulled from the market less than two months later.

Celebrex survived by a 31-1 margin (even though the evidence against it was equally compelling). (The vote still would have been an amazing 21-1 in favor of Celebrex without the 10 “interested” voters).

Although two of the three drugs have been pulled from the market and the third is about to undergo a major safety study, the panel merely recommended all COX-2 inhibitors carry “black box” warnings.

Needless to say, the vote was met with shock and outrage by activists, medical experts, and researchers alike. Several highly reputable news agencies like CBS News, The New York Times, and Forbes, for example, also questioned whether the panel had been “stacked” in favor of the pharmaceutical companies with advisers who had significant “conflicts of interest.”

Undue influence has often been exerted in ways that have compromised the impartial functioning of the FDA and its researchers and doctors.

In 1997 Rezulin was approved to treat Type 2 diabetes. The drug, known generically as troglitazone, was made and marketed by Parke-Davis, a division of Warner-Lambert Company of Morris Plains, New Jersey.
Rezulin was removed from the market by the FDA in March of 2000 as a result of having been linked to a mounting number of cases of serious liver damage and death. The drug had already been removed from the market in England in December of 1997 where officials have refused to allow its reintroduction.

Only eight months after Rezulin was marketed in the United States, the FDA announced that the drug had been linked to illness and death from liver failure. For this reason, the FDA recommended frequent monitoring of liver function in patients taking Rezulin.

Significantly, these problems had been apparent while the drug was being tested according to Dr. Anne Peters, an endocrinologist at the University of California at Los Angeles. Dr. Peters noted that the abnormal test results were so extreme they should have been regarded as a "red flag."

Dr. Peters, and others, believed that Rezulin should have been marketed from the beginning with strong warnings and the requirement that those taking the drug have frequent tests of liver function. Instead, the drug was marketed without any recommendation for liver monitoring.

Unfortunately, the injuries and deaths continued. Surveys showed that few patients were being properly monitored. Labeling changes ordered by the FDA did nothing to remedy the situation and soon, serious divisions developed within the agency itself.
By the beginning of 2000, four senior FDA physicians as well as Dr. Robert I. Mishbin, the FDA Medical Officer most closely involved with the government's approval and continued support of Rezulin, were strongly urging its withdrawal from the market.

In fact, in a January 24, 2000 e-mail to his superiors, Dr Mishbin stated: "I see no reason why any well-informed physician would continue to prescribe [Rezulin]." In warning that "additional cases of preventable liver failure" may occur, Dr. Mishbin also stated that he did not see "any reason why FDA should delay in taking steps to remove [Rezulin] from the market."
The FDA's response was to threaten Dr. Mishbin with disciplinary action or dismissal from federal service.
Although the director of the FDA's drug review center, Dr. Janet Woodcock claimed in a March, 2000 prepared statement that the FDA still believed the benefits of Rezulin to outweigh its risks, a member of the FDA Advisory Committee stated that he was "not surprised" to hear of the dramatic increase of reported liver-failure cases associated with the drug.

Moreover, even long before Dr. Mishbin's change of position, two other FDA physicians had raised serious questions concerning Rezulin. In October, 1996, FDA Medical Officer, Dr. John L. Gueriguian recommended Rezulin not be approved because of potential liver and heart toxicity.

Dr. Gueriguian was the FDA Medical Officer initially in charge of reviewing the Rezulin New Drug Application (NDA). He was a twenty year veteran of the FDA, but was removed from the project in November, 1996, only weeks before the FDA's Medical Advisory Board was set to consider whether to recommend approval of the drug.

The removal came at the request of Warner Lambert, ostensibly because he had used intemperate language in describing the safety and efficacy profiles of the drug. Significantly, this medical Officer had concluded that Rezulin was no more effective in treating diabetes than other drugs already on the market yet it had potential hepatic (liver) and cardiac (heart) side effects.

That same month, Dr. Gueriguian was stripped of further involvement in reviewing Rezulin and his negative review purged from agency files.

In 1999, Dr. David J. Graham, a senior FDA epidemiologist, publicly warned the agency's Advisory Committee that every Rezulin user was at risk for sudden liver failure. In fact, Dr. Graham presented data indicating that, even with monthly monitoring, Rezulin patients still ran the risk of spiraling into sudden liver failure.

Dr. Topol, himself caught up in the problem created by these relationships, announced he would cut all ties to industry, which included relationships with Eli Lilly, deCode Genetics, and the Medicines Company notwithstanding that many doctors at the Clinic and elsewhere have similar consulting deals.

"I think there's a real problem in academics today," he told The New York Times in January 2005. "There's a very close-knit relationship with industry, and it's too close when any individual can derive a profit from that relationship."

A recent survey involving 3,247 scientists who were based in the United States and who had received funding from the National Institutes of Health revealed that about 33% of the participants stated that, within the previous three years, they had engaged in at least one practice that could get them into trouble.

The types of questionable conduct included circumventing minor aspect of rules for doing research on people (8%) and ignoring another researcher’s use of flawed data or questionable interpretation of data (about 13%). Less than 2% admitted falsifying data, plagiarism, or ignoring major aspects of rules governing studies with human subjects. Surprisingly (or maybe not so surprisingly), almost 16% admitted they had changed the designs, methods, or results of a study “in response to pressure from a funding source.”

The National Institutes of Health (NIH) conducted an internal review with respect to consulting payments from pharmaceutical companies to scientists employed by the agency. Of the initial sample, more than half (44 of 81) admitted to conduct which violated one or more NIH rules.

Of those, 36 were still employed by the agency and were referred for possible disciplinary action. Nine of those 36 were also referred to the HHS Office of Inspector general for further investigation. The 8 who left the agency are not subject to administrative action.
The House Energy and Commerce Committee requested the review after comparing NIH records to consulting agreements maintained by 20 pharmaceutical companies. The Committee found 81 cases between 1999 and 2004 where the agreements were not listed in the NIH records provided to the committee.

Excerpts from the findings of the investigation, provided by NIH Director Elias A. Zerhouni to three members of Congress included the following statement: "We discovered cases of employees who consulted with research entities without seeking required approval, consulted in areas that appeared to conflict with their official duties, or consulted in situations where the main benefit was the ability of the employer to invoke the name of NIH as an affiliation.”

Although Zerhouni requested the release to Congress to be treated as confidential, Committee leaders released it as a matter of compelling public interest.

Thus, can anyone really look at the Pfizer (Celebrex) study involving the Cleveland Clinic (without Dr. Topol in the lead) as purely coincidental and beyond the possibility of bias and conflict of interest? Hardly.

If anyone needs additional evidence of the potential for a problematic outcome to this latest study, consider the Washington Post report of August 5, 2001. That article, entitled “Missing Data on Celebrex” (by Susan Okie), sounds eerily similar to the recent revelation by the New England Journal of Medicine (NEJM) with respect to Merck’s conduct involving Vioxx study data.

“When editors of the Journal of the American Medical Association sent medical expert M. Michael Wolfe an unpublished study on the blockbuster arthritis drug Celebrex last summer, he was impressed by what he read.
Tested for six months in a company-sponsored study involving more than 8,000 patients, the drug was associated with lower rates of stomach and intestinal ulcers and their complications than two older arthritis medicines diclofenac and ibuprofen.

JAMA's editors wanted to rush the findings into print, and Wolfe and a colleague provided a cautiously favorable editorial to accompany it. But in February, when Wolfe was shown the complete data from the same study as a member of the Food and Drug Administration's arthritis advisory committee, he said he saw a different picture.
‘We were flabbergasted,’ he said.

The study already completed at the time he wrote the editorial - - had lasted a year, not six months as he had thought, Wolfe learned. Almost all of the ulcer complications that occurred during the second half of the study were in Celebrex users. When all of the data were considered, most of Celebrex's apparent safety advantage disappeared.

‘I am furious I wrote the editorial. I looked like a fool," said Wolfe, a Boston University gastroenterologist. "But all I had available to me was the data presented in the article.’

JAMA's editor, Catherine D. DeAngelis, said the journal's editors were not informed about the missing data. ‘I am disheartened to hear that they had those data at the time that they submitted [the manuscript] to us," she said. "We are functioning on a level of trust that was, perhaps, broken.’

The study's 16 authors included faculty members of eight medical schools. All authors were either employees of Pharmacia, Celebrex's manufacturer, or paid consultants of the company.

***With inclusion of the later data, ‘the actual difference between Celebrex and [the other drugs] are not as wide as they were at six months," he acknowledged. "But I think in the end, it does show that Celebrex has a superior safety profile.’
***Meanwhile, the JAMA article and editorial have likely contributed to Celebrex's huge sales. ‘When the JAMA article comes out and confirms the hype, that probably has more impact than our labeling does,’ said Robert J. Temple, director of medical policy at the FDA's Center for Drug Evaluation and Research.

James Wright, a professor of clinical pharmacology at the University of British Columbia, said he complained to JAMA after noticing differences between the published report and the data presented to the FDA. He praised the Public Citizen's Health Research Group, a consumer organization, for filing a lawsuit that led to the agency's putting all drug studies presented to its advisory committees on its public Web site.

‘Otherwise, we still wouldn't know this,’ Wright said. ‘We would still be in the dark.'

Why should anyone believe that anything has changed so dramatically that the upcoming study will not be prone to the same misgivings by experts and consumer advocates alike? All of the examples set forth above indicate the possibility of another questionable study is more than just a remote possibility especially with Dr. Topol on the outside looking in - the same Dr. Topol who since he came to the Clinic in 1991 has been responsible for establishing its medical school and significantly enhancing the reputation of its cardiovascular medicine unit.

Dr. Topol has revealed that the Clinic’s conflict-of-interest committee, on which he served, had looked into the financial arrangements of other doctors, including Dr. Cosgrove, as well as the fact that patients at the Clinic were being used as subjects in tests of medical devices made by companies in which the Clinic had financial interests.
One potential conflict at the Clinic involved the chief executive of Invacare a major health care supply company. Invacare conducts about $200,000 a year in business with the clinic and several people with Clinic associations sit on the Invacare board.

They include Dr. Bernadine Healy, the former head of the Red Cross who is married to Dr. Floyd D. Loop, the cardiac surgeon who led the Clinic until he retired last year and was replaced by Dr. Cosgrove. Dr. Healy owns options for 41,570 shares of stock in Invacare, according to a securities filing from earlier this year.

As noted above, Dr. Cosgrove is a cardiac surgeon. He is quite familiar with the role physicians play in industry since his inventions include the Cosgrove-Edwards heart device. The device, marketed by Edwards Lifesciences, is used at the Clinic. The Clinic has refused to discuss how or whether its patients are informed of Dr. Cosgrove's connection to the device.

Last January, The New York Times discussed a number of companies in which the Clinic had a financial interest (including AtriCure, a heart device manufacturer).

On December 16, The Wall Street Journal ran a front-page article about the Cleveland Clinic’s financial ties with Cardio Vention, the maker of a heart-lung machine blamed for the death of a Clinic patient in May 2002. Press releases issued by the Clinic through Dr. Cosgrove that praised the device in April 2002, failed to disclose that Dr. Cosgrove and the Clinic had a financial interest in the company that ceased operations in 2003.

Several Clinic surgeons, including Dr. Cosgrove, were consultants to Cardio Vention and received stock options in the company.

Dr. Cosgrove also has financial interests in a number of other companies doing research at the Cleveland Clinic as a result of his investment in Canaan Partners, a venture capital fund that also backed Cardio Vention.
Many medical ethicists believe that all of these entanglements may call into question the Clinic's reputation as a world-class independent research institution. “All of these pieces of information coming out bit by bit are potentially damaging to the clinic's reputation," said Dr. Mildred K. Cho, a medical ethicist at Stanford University.
Although the clinic claims its board of trustees has appointed an independent group to review the Clinic's conflicts, Dr. Topol has been removed from the conflict-of-interest committee, a position he held by virtue of his leadership role at the medical college.

Thus, as the COX-2 saga continues to unfold (or unravel as the case may be) will the Celebrex study live up to the hype already placed on it by Dr Nissen who has stated: "There's only one way through good science. We know the burden is upon us to do this right."

Independent researchers are to collect and control the results and have offered to make all of them public, not only the final conclusions. None of the top researchers will be permitted to have financial ties to any pharmaceutical company that manufactures painkillers.

The Celebrex study will be called PRECISION, for Prospective Randomized Evaluation of Celecoxib Integrated Safety versus Ibuprofen or Naproxen. Results are expected in about four years. You can sell an awful lot of Celebrex in four years, that’s for sure.

Health Canada Bans Sale of Bextra

Sun, 18 Dec 2005 00:00:00 -0800

The era of the COX-2 inhibitors appears to be coming to an end. Vioxx was removed from the market worldwide by Merck in September 2004. Pfizer has announced Celebrex is about to undergo new safety testing while the company’s other COX-2 inhibitor, Bextra, was removed from the market in April 2005.

The suspension of Bextra sales was due to safety concerns related to rare but serious skin reactions and cardiovascular problems. At that time, Health Canada issued a stop-sale order which ensured that Bextra (valdecoxib) would not be permitted to return to the Canadian market without further consultation with Health Canada.

The Canadian agency, which is the equivalent of the U.S. FDA, studied all of the available data on COX-2 inhibitors in general and concerning Bextra, specifically. Based on that review Health Canada has determined that “there is an increased risk of heart attack and stroke when these drugs are used for long-term treatment. Studies also showed that these side-effects can occur when Bextra is used for short-term pain relief following high-risk heart surgery. Bextra is also associated with a risk of rare but severe and potentially fatal skin reactions.”

The official announcement on the agency’s Web site (http://www.hc-sc.gc.ca/ahc-asc/media/advisories-avis/2005/2005_134_e.html) states: “The decision to stop the sale of Bextra is based on information submitted by the manufacturer, Pfizer Canada Inc., and consultations with external experts and the public. Health Canada concluded that there is insufficient evidence to establish the safety of the drug for its recommended use.”

“As a result of this regulatory action, the manufacturer will not be able to bring Bextra back onto the Canadian market under its present conditions of use. Health Canada has sent a letter to inform Pfizer Canada Inc. of the status of Bextra.”

The advisory concludes by stating that: “Health Canada has completed the review and agrees with the panel that available evidence indicates that COX-2 selective inhibitors and all other non-steroidal anti-inflammatory drugs are associated with an increased risk of cardiovascular events when high doses are used for long periods. However, the exact nature of that increased risk may differ from one product to another. The panel also found that the overall risk versus benefit profile for Bextra does not support the marketing of this drug in Canada under its current conditions of use.”

Health officials won't revive arthritis drug

Sat, 17 Dec 2005 00:00:00 -0800

Bextra, an anti-inflammatory drug for arthritis sufferers, will not be allowed back on the Canadian market.

Based on recommendations from an expert safety panel, Health Canada said yesterday the cardiovascular risks of the drug, including heart attack and stroke, outweighed its benefits.

Officials said it also causes rare but severe and potentially fatal skin reactions more often than other drugs in its class.

"We concluded that there is insufficient evidence to establish the safety of the drug for its recommended use," said spokesperson Jirina Vlk.

Bextra was withdrawn voluntarily from the market in April by drug giant Pfizer after severe skin reactions affected seven people in Canada.

The drug falls into the same controversial class of drugs as Vioxx and Celebrex, known as cox-2 inhibitors. Vioxx, once the most popular painkiller in Canada, was pulled from the worldwide market in September 2004.

New warnings of cardiovascular risks have subsequently been issued for Celebrex.

In a written release, Pfizer Canada said "Bextra is an important treatment option ... (and) it should continue to be available for those patients who could benefit from it."

A Health Canada expert safety panel issued a report last summer recommending Vioxx be allowed back on the market.

However, panel members in an 8-5 vote said Bextra should not be. Bextra was approved for sale in December 2002 and 665,783 prescriptions were filled in Canada last year.

New Study Finds COX-2 Inhibitors Are Not Safer for the Stomach

Mon, 05 Dec 2005 00:00:00 -0800

A new report in the December 3 issue of the British Medical Journal finds that COX-2 inhibitors are just as harmful to the stomach as traditional anti-inflammatory medications like aspirin. This finding would negate the central reason the embattled family of drugs was approved in the first place.

Researchers at the University of Nottingham examined cases of 9,407 patients with upper gastrointestinal events, like stomach bleeding or stomach ulcer, from 367 general practices. 45% of the patients had received traditional non-steroidal anti-inflammatory drugs (NSAIDs), and 10% had received COX-2 inhibitors. Out of 88,867 control subjects, 33% had been given an NSAID, and 6% had been given a COX-2 inhibitor.

It was found that there was an increased risk of stomach problems with both types of pain killers. The risk was significantly higher for the COX-2 inhibitors naproxen, and rofecoxib (Vioxx), and diclofenac (Voltaren). The risk was slightly lower for celecoxib (Celebrex). Celebrex is the only COX-2 inhibitor that is still on the market in the U.S. since the others were pulled as a result of cardiovascular and other potential adverse reactions.

The report authors concluded that even though COX-2 drugs were designed to provide pain relief without the serious gastrointestinal side-effects associated with conventional NSAIDs, "we found no consistent evidence of enhanced safety against gastrointestinal events with any of the new cyclo-oxygenase-2 inhibitors [cox-2 inhibitors], compared with non-selective, nonsteroidal, anti-inflammatory drugs."
Dr. A Mark Fendrick, professor of internal medicine and health management and policy at the University of Michigan, believes that this study illuminates the increased dangers of gastrointestinal (GI) bleeding when a COX-2 inhibitor and aspirin are used together.

According to Dr. Fendrick: "The fact that cox-2 inhibitor drug users had higher rates of adverse GI events than nonusers comes as no surprise to me, Even a drug that might be safer than other alternatives doesn't mean that the drug is completely safe." It is fine to take a cox-2 inhibitor for joint pain and an aspirin for your heart, but “when you combine these two, they really present GI problems."

Another expert, Dr. Eric Matteson, a professor of medicine at the Mayo Clinic College of Medicine in Rochester, Minnesota, believes the study reveals COX-2 inhibitors increase the risk of GI bleeding and ulcers when used in clinical practice. "These drugs were touted as prevention of adverse GI events, which is completely false. There might be some reduction in risk, but it was never prevention."

"In actual practice, the utility of these drugs is very low in terms of reducing the risk for important GI side effects," Matteson said. "This differs from what was found in clinical trials, which is always different from what is seen in actual practice." According to Matteson this study highlights the GI risks of taking any of these drugs. "All NSAIDs increase your risk for stomach problems, including ulcers and bleeding, which can be serious and even fatal. This includes the COX-2 drugs."

Of course, if this is so, all of the hype and expense associated with the COX-2s was for naught and the only ones that benefited from the drugs were (and are) Merck and Pfizer, which have made tens of billions of dollars in profits from Vioxx, Celebrex, and Bextra.

Many Painkiller Users Not Protected Against Stomach Bleeding

Mon, 10 Oct 2005 00:00:00 -0700

A new study finds that less than a third of patients at high risk for gastrointestinal bleeding while taking NSAID painkillers are being prescribed medicines to prevent that bleeding.

NSAIDs include over-the-counter and prescription versions of aspirin, ibuprofen and naproxen (Aleve), as well as Vioxx and Bextra, which have been recalled, and Celebrex, which is still sold in the U.S.

According to ABC News, doctors have long recognized that long-term use of NSAIDs can raise risks for gastrointestinal bleeding, and guidelines exist to spot patients at high risk. However, many doctors are not giving patients the medicines that can protect them against bleeding, according to study author Dr. Neena S. Abraham, a gastroenterologist at Baylor College of Medicine

NSAIDs are the most commonly prescribed drug in the United States, says Abraham, and upper gastrointestinal bleeding occurs in about 4.5 percent of patients who take NSAIDs over the long term. Those most at risk for bleeding include people over 65, patients who take steroids or anti-coagulants with NSAIDs, and those who take painkillers in an amount exceeding the manufacturer’s recommended dosage.

In their study, Abraham and her colleagues looked at more than 300,000 patients treated throughout the county in 2002. All were prescribed NSAIDs for pain relief, and would also be considered at high risk for upper gastrointestinal bleeding.

Among patients with one or more risk factors, only about 27% were given therapy to counter the risk of bleeding, the researchers found. Among patients with two or more risk factors, the number rose to 40% and therapeutic assistance reached a high of 42% for those with three or more risk factors for bleeding.

The results of the study appear in Gastroenterology 2005.

Merck Loses Vioxx Case

Fri, 19 Aug 2005 00:00:00 -0700

DOBBS: A jury tonight in Texas finding Merck liable for the death of a man who took its blockbuster painkiller drug Vioxx.

The jury awarded his widow more than a quarter of a billion dollars in damages after reviewing evidence that links the drug to an increased risk of heart attack and stroke. This is the first of thousands of Vioxx-related lawsuits slated for trial. Ali Velshi is here now.

Ali, this award is unbelievable.

ALI VELSHI, CNN CORRESPONDENT: It's phenomenal. It's also not like to stand up. The widow of the man who is in question here has actually -- her lawyer said he doesn't expect this award of $229 million in punitive damages to stay because under Texas law, they don't allow it. That 229 is probably going to come down to $2 million.

DOBBS: Do we know what inspired the jury to come up with such a massive number?

VELSHI: The issue is how the drug companies market these drugs. The information was out there that they have risks, but here's the issue. These are competitive drugs to Vioxx.

VELSHI: extra pain killers. And this is the stuff that comes with it. The drug companies say, "we put this out there. This is the information that you need to read." But who reads it? Do we read it? Should we read it? The issue is that Merck marketed this drug with the benefits and focus and the risks.

DOBBS: And a point of fact, Bextra, Celebrex, and Vioxx, Vioxx taken off the market, these for a short period, the FDA ultimately being criticized roundly for permitting these COX-2 inhibitors to be on the market at all. Several scientists saying they're simply not safe. But the lack of safety justified because of the immense pain that apparently some of these drugs, apparently I say underlined, relieve. So it's a remarkable situation.

VELSHI: Vioxx with a $2.5 billion a year drug. Lipitor is a $10 billion a year drug. But these drugs all come with risks, and everybody has to weigh the good against the bad. And the issue is how much information do you need to make that decision.

DOBBS: And Merck's stock, as one might expect, plummeting today.

VELSHI: It took a big hit today. But it took a big hit when they pulled it off the first time. So Merck is a smaller company than it once was.

DOBBS: OK. With 4,000 lawsuits in the wings...

VELSHI: This is where people are worried. Might be up to $50 billion in liabilities some analysts say. We'll find out more as this unfolds.

DOBBS: Indeed we will. Ali Velshi, thank you.

Vioxx Decision

Fri, 19 Aug 2005 00:00:00 -0700

BLITZER: There's breaking news we're following right now in a major drug liability case, a Texas jury only moments ago has just found the giant pharmaceutical company, Merck, responsible for the death of a man who took their now pulled painkiller Vioxx.

Our Business Correspondents Ali Velshi and Allan Chernoff both standing by with details of what has just happened, let's start with you, Allan. What happened?

ALLAN CHERNOFF, CNN SENIOR CORRESPONDENT: Wolf, this is a huge defeat for Merck because on the face it appeared that this actually was a relatively weak case against Merck, the pharmaceutical giant.

You'll recall that Merck had withdrawn Vioxx last year after studies showed it could cause heart attacks or stroke in people who took the drug for more than 18 months.

Well, the person who passed away here back in April of 2000, Bob Ernst, had taken the drug for only eight months and he did not have a heart attack or a stroke according to the coroner. Nonetheless, the jury here has found Merck liable for his death and awarded his widow a total of $253 million, $24 million of that in mental anguish, $229 million of that punitive damages against Merck.

Bob Ernst, the person who passed away, he was a manager at a Wal- Mart, so he did not have a very large salary at all. Nonetheless, a huge victory for the plaintiffs here, Merck suffering a major defeat and this really could open the floodgates for more lawsuits against Merck regarding Vioxx.

There are already about 4,000 lawsuits against the company and this clearly would encourage other people to file suit against Merck, a big defeat for the pharmaceutical company, Wolf.

BLITZER: Allan, stand by.

Ali Velshi has also been following this very important trial. Ali, give us your thoughts on what has just happened.

ALI VELSHI, CNN CORRESPONDENT: I think Allan put his finger on it. This wasn't thought to be as big a deal as it was for Merck because there are a lot more of these lawsuits following it. This is not good news for Merck but it seems to the markets seem to be reacting in a way that expected it.

Allan, one of the things about Texas is the old Fen-Phen trial, the old American Home Products, which has now become Wyeth. There was a $900 million punitive award, punitive damages awarded to the plaintiffs there.

Texas has a law that caps punitive damages. It's typical that this kind of thing would be pared down that the punitive damages of 200-plus million dollars is probably going to be pared back.

CHERNOFF: Sure, most likely that that number would be pared down without question but here clearly the big news is that Merck has lost the case and this was a case that on the surface, again, Merck seemed to have a very simple argument and it clearly would have argued that Bob Ernst simply didn't apply, wasn't one of these people who should have been a victim of Vioxx according to Merck's scientific studies.

But, the jury has clearly gone against Merck and a huge victory for the attorney Mark Lanier. He's a relative young man but considered one of the top litigators in the country and he took this case on several years before Merck had pulled Vioxx from the market. After Merck did pull Vioxx then the flood of lawsuits came in. So, Wolf, again we're going to really see a lot more lawsuits being filed now against Merck. There's no question about that.

BLITZER: Ali, before both of you wind up just remind our viewers about this controversial painkiller Vioxx. Merck on its own voluntarily pulled this painkiller in the face of some studies.

VELSHI: Yes. The issue is how much Merck knew about the dangers associated with Merck with Vioxx. It's a painkiller. It was widely prescribed as an arthritis drug but it was commonly prescribed to people as a sort of a more effective drug than the over-the-counter painkillers that were out there.

Well, what happened is it turns out that after some people suffered heart attacks the investigations led to some understanding that Merck might have known there was a risk and not and as limited as that risk may have been not clearly articulated that risk to people who bought and used the drug regularly. It did become a very popular painkiller.

It's a class of painkillers. There are other ones on the market that were also pulled as a result of it. The issue here is how much pharmaceutical companies have to disclose in terms of the risks that they know of when they market a drug like this, Wolf.

BLITZER: All right, Ali and Allan stand by. We're going to get back to both of you during the course of this program.

And just to recap, a Texas jury has ruled against the giant pharmaceutical company Merck and Company, liable now for $253.4 million damages and other expenses, the result of the once very popular painkiller Vioxx, more on the story coming up.

FDA Gives Celebrex New Warning Label and New Indication

Wed, 03 Aug 2005 00:00:00 -0700

In a bureaucratic mixed message, the FDA finalized a long-anticipated black box warning for the Celebrex (celecoxib) label on the same day that the agency approved the drug for ankylosing spondylitis, a new indication.

In April, an independent panel of advisers convened by the FDA recommended the black box warning for Celebrex and other NSAIDs, including ibuprofen and naproxen. The panel was convened after published reports that Cox-2 inhibitors such as Celebrex increases the risk of cardiovascular events.

Last September, Merck withdrew its popular Cox-2 Vioxx (rofecoxib) from the market after investigators in a cancer-chemoprevention trial reported that long term use of the drug increased the risk of heart attacks and strokes, although it did not increase cardiovascular mortality. Earlier this year, Pfizer, which makes Celebrex, withdrew its other Cox-2, Bextra (valdecoxib), when similar reports surfaced about it. Celebrex is the only Cox-2 remaining on the market.

The Cox-2 cardiovascular risk link prompted researchers to review studies of other NSAIDs, which turned up apparent increased cardiovascular events associated with those drugs as well. The bottom line, the FDA advisory group concluded, was that all the painkillers with the exception of aspirin should receive new labels to reflect the increased risk.

Celebrex's label will recommend that the drug be prescribed at the lowest dose and shortest time possible. The label will also carry a warning that Celebrex should not be used to treat pain associated with heart bypass surgery.

In announcing agreement with the FDA over the new label, Pfizer said the agency approved Celebrex for ankylosing spondylitis, or arthritis of the spine, which affects about 400,000 Americans. With the new indication, Celebrex is now approved for treatment of osteoarthritis, rheumatoid arthritis and as a treatment for familial adenomatous polyposis.

New Study Links Common Painkillers with Heart-Attack Risk

Thu, 09 Jun 2005 00:00:00 -0700

Ibuprofen and other non-steroidal anti-inflammatory drugs (NSAIDS) may increase the risk of heart attack, according to research published in this week's BMJ.

Patients should not stop taking the drugs involved, the authors caution, but further investigation into these treatments is needed, they say.

In the biggest study of its kind to date, researchers identified 9,218 patients across England, Scotland and Wales who suffered a heart attack for the first time over a four-year period. Patients ranged in age from 25 to 100.

The investigators looked at the prescribing patterns for these patients, tracking whether and when they had been prescribed NSAIDS. This class of medications, which commonly are prescribed to relieve inflammation and pain, includes ibuprofen, diclofenac (Advil, Motrin, etc.), naproxen (Aleve, Nuprin, etc.), celecoxib (Celebrex) and rofecoxib (Vioxx) plus a host of other less commonly prescribed anti-inflammatories.

Rofecoxib is no longer commercially available, having been withdrawn from the market in 2004. NSAIDS Increased Risk

The findings were adjusted to allow for several other heart-attack risk factors including age, obesity and smoking habits. Importantly, the researchers also adjusted for whether patientd already suffered from heart disease or were prescribed aspirin.

For those who were prescribed NSAIDS in the three months just before the heart attack, the risk increased compared with those who had not taken these drugs in the previous three years, the researchers found. For ibuprofen, the risk increased by almost a quarter (24%) and for diclofenac, it rose by over a half (55%).

The newer generation of anti-inflammatories known as COX-2 inhibitors also were associated with increased rates of first-time heart attack. Those patients who were prescribed the drugs in the preceeding three months were at 21% higher risk of heart attack if taking celecoxib (Celebrex) and 32% increased risk if taking rofecoxib (Vioxx).

'Considerable Implications for Public Health'

Since this study was concluded, rofecoxib was withdrawn due to concerns over heart-attack risk. That makes the impact of this study on patients even more important, say the authors, since those previously taking rofecoxib will have turned to the other anti-inflammatories in greater numbers.

The most significant findings were for the drugs ibuprofen, diclofenac and rofecoxib, say the authors. In terms of "numbers needed to harm" in the 65 and over age group, for those taking diclofenac, one extra patient for every 521 patients was likely to suffer a first-time heart attack.

For rofecoxib, the figure was one patient for every 695 patients; and for ibuprofen, one patient for every 1,005 patients was at risk.

"Given the high prevalence of the use of these drugs in elderly people and the increased risk of myocardial infarction [heart attack] with age, the relatively large number of patients needed to harm could have considerable implications for public health," say the authors.

The nature of this report, an observational study may make it prone to other explanations for the findings, say the authors. "However, enough concerns exist to warrant a reconsideration of the cardiovascular safety of all NSAIDS," they conclude.

Penn Study Points To How COX-2 Inhibitors Can Eventually Lead To Heart Disease

Wed, 25 May 2005 00:00:00 -0700

University of Pennsylvania School of Medicine researchers have found additional evidence that may help explain how selective inhibitors of COX-2 might predispose individuals to heart disease and stroke.

In Circulation Research, they report that a COX-2-derived fatty substance a prostaglandin called prostacyclin controls the blood-vessel response to stresses such as high-blood pressure, thereby further linking COX-2 inhibitors to an increased risk of heart attack or stroke.

This knowledge, along with a growing literature on physiological responses to COX-2 inhibitors, should help in the development of a rational approach to clinical risk management for this class of drugs.

Two randomized trials of COX-2 inhibitorsthe gold standard of clinical evidenceconducted in 2004 at other institutions suggested that risk of cardiovascular disease might increase gradually during continued treatment with drugs such as Celebrex and Vioxx, even in individuals initially at low risk of the disease.

"The risk of heart attack and stroke became progressively evident during treatment with either Celebrex or Vioxx during the APPROVe and APC trials last year," says Garret FitzGerald, MD, lead author of the study published online last week. FitzGerald is the Director of the Institute for Translational Medicine and Therapeutics at Penn.

These studies were designed to determine whether COX-2 inhibitors limited the development of benign growths in the large bowel of patients whoto the best of study authors' knowledgewere at low risk of heart disease. "While the results of these trials are not conclusive, they are compatible with a gradual transformation of increased cardiovascular risk during continued dosing with either Celebrex or Vioxx," says FitzGerald. "We need to determine how this might occur, and whether we can manage this risk by developing tests that reflect the process."

Earlier animal studies by Penn researchers and others showed that suppression of the protective fat prostacyclin, which is made by COX-2, could predispose individuals to a rise in blood pressure which, in turn, can accelerate hardening of the arteries, or atherosclerosis. COX-2 inhibitors such as older NSAIDs have been shown to raise blood pressure in people. In addition, the Penn group has shown in previous studies that shutting down prostacyclin hastens initiation and early development of atherosclerosis.

The current research expands on this notion. R. Daniel Rudic, PhD, and Derek Brinster, MD, and others in FitzGerald's laboratory, report that COX-2-derived prostacyclin also controls the changes that occur in the muscular lining of blood vessels in response to pressure-related changes in blood flow.

They used two animal models to test their ideas. In one, they looked at changes in a blood vessel that had been transplanted into mice of a different genetic make-up; in fact, the model mimicks the events of human organ transplant rejection. Here, they found that they had, in effect, removed a brake on the response of the blood vessel to the challenge of transplantation by deactivating prostacyclin by genetically deleting its receptor.

The result was that muscle cells proliferated dramatically, which normally reduces the openness of the blood vessel. However, the openness of the blood vessel was not changed, through a process of structural reorganization of the blood vessel called vascular remodeling.

In the second model, they reduced blood flow in arteries in the neck and looked at the downstream effects in the blood vessel. This time, instead of suppressing prostacyclin receptor signaling by genetic deletion, they did so by giving a COX-2 inhibitor. Indeed, they saw the same effect.

Cells in the muscular lining of the vessel wall multiplied (just like in the transplant model). Additionally, despite the vessel growth caused by the COX-2 inhibitor, openness of the blood vessel was again preserved. This occurred despite lower blood flow caused by the COX-2 inhibitor. Thus, prostacylin may act to remodel blood vessels to preserve adequate blood flow.

"What is really convincing here is how similarly the two models responded and how the genetics of the pharmacological approach to disrupting the effects of COX-2 had the same effect," says Rudic. In further studiesalso described in the paper and performed in collaboration with Thomas Coffman, of Duke UniversityFitzGerald's group showed that the consequences of shutting down COX-2-derived prostacyclin could be limited, in part, by removing a receptor activated by thromboxane A2, the fatty product of COX-1 in platelets.

This mirrors a similar balancing effect between COX-1 and COX-2, which has been noted in the case of blood clotting, blood pressure, and atherosclerosis. This suggests that suppression of thromboxane with low-dose aspirin could reduce the risk of heart disease if taking COX-2 inhibitors.

These findings suggest that during prolonged dosing with COX-2 inhibitors, several consequences of drug actiona rise in blood pressure, initiation, and early development of atherosclerosis, and now the architectural and functional response of blood vessels to such stresscould all interact in a reinforcing fashion to transform the risk of heart attack and stroke, even in previously healthy individuals. "We need to determine whether these mechanisms are operative in people, and if so, we should be able to develop tests which reflect this process," says FitzGerald.

"This may allow us to detect the small number of individuals at risk of rapidly developing heart disease and stop the drugs before they run into trouble. We could also determine how quickly risk might dissipate on stopping the drugs. Certainly, the development of a rational approach to risk management will be key to giving Celebrex or other COX-2 inhibitors safely, even to healthy patients, for extended periods."

Perils of Pain Relievers Often Disguised In Tiny Type

Sun, 08 May 2005 00:00:00 -0700

If ever there was a classic case of "no free lunch," popular pain control medications are it. There's not one without a potentially serious risk. Yet, far too many people use them carelessly, without adequate attention to dosage and warnings about possible risks.

For over a century, aspirin was the pain drug of choice, until data emerged on the rather large number of bleeding-related deaths this time-honored medicine caused each year. In fact, many pharmaceutical experts say that if aspirin had to go through the Food and Drug Administration's approval process today, it would never make it to market.

Along came some dandy substitutes, now also sold over the counter under brand names and as generics: ibuprofen (Advil, Motrin IB) and naproxen (Aleve). Ibuprofen and naproxen, known as nonsteroidal anti-inflammatory drugs, or Nsaids, can equal or outdo aspirin's action against painful inflammation but at less risk of bleeding.

But they, too, can have serious side effects: They can irritate the gastrointestinal tract and possibly cause ulcers. People who use Nsaids chronically are often told to take an anti-acid drug to protect their stomachs.

This problem opened up a market for a new kind of drug called a cox-2 inhibitor, sold as Celebrex, Vioxx, Bextra and Mobic. These drugs are as good or better than ibuprofen for pain, although as patented prescription medications they greatly multiplied the cost of pain relief.

The cox-2 inhibitors were considered safer because they reduced the risks of bleeding and gastrointestinal damage. And as major money-makers, they were heavily promoted, especially to the millions who need relief for chronic problems.

Alas, these too have come under serious fire as their use mushroomed and evidence emerged linking them to heart attacks and strokes among users already at risk for these problems. With many multimillion-dollar lawsuits looming, Vioxx was the first to be withdrawn from the market, recently followed by Bextra. Both drugs may come back, accompanied by more stringent warnings. Or their cox-2 cousins, Celebrex and Mobic, may join the ranks as drugs gone by.

Problems also accompany other prescription painkillers, like the opioids.

This brings us to an entirely different drug, acetaminophen, long used to counter fever and occasional aches and pains such as tension headaches. But now acetaminophen is being hailed as an excellent first choice for the relief of chronic pain.

Acetaminophen, often referred to by its most popular brand name, Tylenol, has no anti-inflammatory action. Nor does it cause bleeding or gastrointestinal distress. Many pain specialists say it should be considered first for relief for the persistent pain of osteoarthritis and prolonged pain of muscle or joint injuries.

All in all, acetaminophen is a safe drug for children and adults. Despite the many millions of doses taken by Americans each year, few reports of serious side effects emerge when acetaminophen is used in the dosages recommended by manufacturers.

For example, in a study published a decade ago evaluating the experience of 28,130 children who had taken acetaminophen, there was no increased risk of gastrointestinal bleeding, kidney failure, life-threatening allergic reactions or Reye's syndrome, a potential fatal side effect of aspirin when given to children with viral infections.

Acetaminophen is also considered safe for women who are pregnant or breast-feeding, although they are advised to check first with their doctors. And acetaminophen is the pain reliever of choice for those with serious allergies who may be at risk of severe allergic reactions from aspirin and Nsaids.

Perhaps as a testament to its safety, acetaminophen is found not only on its own in a variety of dosages, but also in combination with other medications, over the counter and prescription. If consumers are unaware of its presence in different medications, or if they fail to adhere to cautionary statements about dosages, it is possible to take too much acetaminophen inadvertently.

As with any other medicine, with acetaminophen it is critically important to keep in mind this irrefutable adage: The dose makes the poison.

For example, no one questions the safety of following recommended doses. If you can read the fine print on the label, it will tell you that for adults and for children 12 and older, two 500-milligram tablets or capsules can be taken every four to six hours, as long as no more than eight tablets (a total of 4,000 milligrams) are taken in a 24-hour period unless a physician says otherwise.

Taking more than 4,000 milligrams a day of acetaminophen on a chronic basis can damage the liver of an adult. The danger dose would be far smaller for young children.

It is easier than you may think to take more than 4,000 milligrams a day. With the higher-dose tablets (650 milligrams each) now sold to treat arthritis, you can easily exceed the safety limit if you do not follow the instructions to take two tablets every eight hours, for a maximum daily dose of six tablets in 24 hours, adding up to 3,900 milligrams a day.

Even if you follow these directions, you can exceed the recommended daily dose if you also take another medication say, an over-the-counter cold or flu remedy that contains acetaminophen.

The label on Tylenol Arthritis Pain has a clearly stated warning: "Do not use with any other product containing acetaminophen." But without a magnifying glass, many elderly people who are the most likely users of an arthritis drug would have trouble reading the labels on this and many other medicines like it.

A second warning on acetaminophen says: "If you drink three or more alcoholic drinks every day, ask your doctor whether you should take acetaminophen or other pain relievers/fever reducers. Acetaminophen may cause liver damage."

So, if your liver is already under attack from alcohol, acetaminophen can be that last straw, resulting in liver failure.

This year, the journal Emergency Medicine warned physicians about the hazards of overdoses of acetaminophen. Dr. Shirley Kung and Dr. Kennon Heard wrote that acetaminophen poisoning could often be much worse than it seemed at first.

Nausea and vomiting can progress to complete liver failure in as little as 24 hours unless the problem is promptly recognized and the proper antidote given within 24 hours of a toxic dose. To fully prevent liver injury, the antidote should be given within eight hours.

Each year, more than 100,000 calls related to acetaminophen are made to poison control centers in the United States, and about 150 acetaminophen-related deaths are reported. Some cases result from deliberate overdoses by people trying to commit suicide. But many others are accidental, like the one described in the journal: an 18-month-old child with a fever and cough for three days who had been given acetaminophen every two to four hours.

Other cases result when people whose livers are damaged by other disease take acetaminophen for respiratory infections or pain.

Could Celebrex Survive A Black Box?

Thu, 05 May 2005 00:00:00 -0700

The black box label is the most potent warning in the Food and Drug Administration's arsenal, but it is not necessarily a death knell for drug sales, analysts say.

The label, second only to pulling the drug from the market, can impact sales but it depends on how badly the drug is needed, and this could be good news for Pfizer, analysts say.

The FDA said April 7 it was considering a black box label for Pfizer's blockbuster Celebrex, an arthritis painkiller with $3.3 billion in 2004 sales. On the same day, the agency asked Pfizer to withdraw its other arthritis drug, Bextra, which had $1.3 billion in 2004 sales. Just six months before, on Sept. 30, Merck withdrew Vioxx. All three of these drugs are in the same class of cox2 inhibitors and have been blamed for heart attacks and strokes.

"Definitely [Celebrex] sales are going to be impacted by the formalization of the black box," said Sena Lund, analyst for Cathay Financial. "Physicians do not ignore black box warnings because it becomes a matter of liability."

However, Lund said the loss of sales would be tempered by a lack of competition, with Celebrex's status as "the only cox2 in the market."

Andrew McDonald, research analyst for ThinkEquity Partners, said that black box warnings for many drugs "seriously impair drug sales," partly because physicians fear malpractice suits.

"Doctors, when they see a black box warning, it really makes them anxious in that they can imagine themselves, if an adverse event occurs, in a courtroom trying to explain to a judge why they prescribed the medicine when it says right on the label why it shouldn't be prescribed," said McDonald.

But the fear of liability is reduced in situations when the drug is the only treatment available. "If there aren't alternative therapies, then the drug will continue to do well in the marketplace," said McDonald.

The FDA, physicians and patients weigh benefits versus risks when making decisions about drugs, and when a drug offers a unique benefit, it gains an edge.

Cisapride, a treatment for severe nighttime heartburn, was given an black box warning by the FDA in 1995, and an expanded black box warning in 1998, because it was blamed for heart disorders resulting in deaths. Janssen Pharmaceutica withdrew it in 1999 after totaling $1 billion in sales for that year, said McDonald.

"This is a drug that, despite a warning, was still a phenomenal seller," said McDonald, referring to Cisapride.

A similar situation occurred when Remicade, a treatment for rheumatoid arthritis and Crohn's disease, received a black box warning. Remicade, a drug made by Centocor, can cause serious infections, according to the FDA. But McDonald said the drug is still a strong seller, totaling $2 billion in 2004 sales. (See correction.)

"In this case, the sales have not been terribly affected," said McDonald, referring to Remicade. "The needs for the drugs outweigh the risks associated with them. There's a similar story with Celebrex, in that there aren't very good alternatives."

Association of Bextra (valdecoxib) Tablets Serious Adverse Drug Reactions

Thu, 21 Apr 2005 00:00:00 -0700

Dear Health Care Professional,

On 7 April 2005, Pfizer Canada Inc., following discussions with Health Canada, agreed to voluntarily suspend the sale and marketing of BEXTRA (valdecoxib) tablets in Canada pending the submission of BEXTRAs benefit/risk assessment. Health Canadas request to suspend the sale of BEXTRA is based on the risk of serious, potentially life threatening skin reactions associated with BEXTRA and its ongoing cardiovascular safety assessment of COX-2 inhibitors. Satisfactory safety evidence will need to be established with respect to the review of cardiovascular, gastro-intestinal and rare, but potentially life-threatening skin reactions (Stevens-Johnson Syndrome (SJS), Toxic Epidermal Necrolysis (TEN), erythema multiforme).

As a further precautionary measure, and pending finalization of Health Canadas ongoing cardiovascular safety assessment of COX-2 inhibitors, on 8 April 2005 Pfizer Canada Inc. proceeded with a voluntary recall of all lots of BEXTRA (valdecoxib) oral tablets, 10 mg and 20 mg on the Canadian market.

Pfizer has also agreed to similar suspension of BEXTRA sales and marketing activities in the United States at the request of the Food and Drug Administration and in Europe at the request of the European Medicines Agency (EMEA). Furthermore, in the U.S., on 7 April 2005, FDA announced a series of important changes pertaining to the labeling and marketing of the NSAID group of drugs including COX-2 inhibitors.

Advice to Health Care Professionals

Prescribers are advised:

Not to initiate treatment of new patients

To switch patients to alternative therapy where appropriate

Pharmacists are advised:

Not to dispense further prescriptions for BEXTRA

To advise patients taking BEXTRA to return to their physicians to discuss discontinuing their current treatment with BEXTRA medication and to discuss alternative therapies.

After having consulted with a physician, consumers should return the product to their pharmacy. In order to avoid contaminating ground or municipal water systems, the product should not be flushed down the toilet or sink.

Health Canada is conducting an ongoing cardiovascular safety review of the COX-2 selective NSAIDs. Safety updates were recently communicated to healthcare professionals on the cardiovascular safety and warnings on serious skin reactions associated with BEXTRA as follows:

On 10 December 2004, contraindications for patients undergoing CABG surgery and additional information and warnings on the occurrence of serious skin reactions were introduced (Dear Healthcare Professional Letter:

This previous letter to health professionals outlined specific concerns regarding safety issues for patients undergoing coronary artery bypass graft (CABG) surgery, patients using BEXTRA in any peri and/or post-operative settings, and serious skin reactions associated with BEXTRA, and advised caution in prescribing BEXTRA to patients with a history or risk of cardiovascular disease.

BEXTRA received market authorization in Canada in December 2002, as a selective COX-2 inhibitor, indicated for the symptomatic treatment of osteoarthritis, rheumatoid arthritis and primary dysmenorrhoea.

The original Product Monograph included information regarding the occurrence of rare cases of serious skin reactions and cases of hypersensitivity reactions in patients with or without a history of allergic-type reaction to sulfonamides. A Dear Healthcare Professional Communication was also issued upon introduction of BEXTRA on the Canadian market in order to advise healthcare professionnals of the occurrence of rare cases of serious skin reactions and cases of hypersensitivity reactions in patients with and without a history of allergic-type reactions to sulfonamides.

Pfizer is continuing to monitor the safety of the COX-2 selective NSAIDs, and will review all new data as it becomes available and continue its dialogue with Health Canada. Pfizer will explore options under which the company might be permitted to resume making BEXTRA available to physicians and patients.

Health Canada continues to evaluate the safety of all COX-2 selective NSAIDs in light of recent concerns regarding cardiovascular risk associated with the use of these agents.

Celebrex: Cardiovascular Risk Similar to Vioxx - IMMP Study

Fri, 15 Apr 2005 00:00:00 -0700

Patients taking the arthritis drug Celecoxib (Celebrex) have a similar risk of heart attacks and stroke as those taking the withdrawn drug Rofecoxib (Vioxx), according to a new study by the New Zealand Intensive Medicines Monitoring Programme(IMMP).

Rofecoxib was withdrawn from the market worldwide because of concerns relating to cardiovascular safety.

There is conflicting evidence as to whether Celecoxib, an alternative to Rofecoxib, carries the same cardiovascular risks.

This study's aim was to compare the incidence of thrombotic cardiovascular events in patients taking Celecoxib with patients taking Rofecoxib.

The University of Otago study is an interim analysis following up approximately 11,000 of the 60,000 patients prescribed either medicine during 2001.
Patients’ doctors were asked to supply information about adverse clinical events that occurred since being prescribed the drugs.

The total cohorts included 26 403 patients receiving Rofecoxib and 32 446 patients receiving Celecoxib. 4882 (18%) Rofecoxib and 6267 (19%) Celecoxib patients had been completely followed up.

The unadjusted hazard ratio for Celecoxib compared with Rofecoxib was 1.07.
After adjustment for age this hazard ratio was 0.94.
Further adjustment for sex, ‘as required’ use, indication for use, concomitant NSAID use and pre-existing cardiovascular disease resulted in only minor changes to the hazard ratio.

According to authors, this interim analysis of the Intensive Medicines Monitoring Programme data suggests that in ‘real-life’ postmarketing use in New Zealand there is no significant difference in the risk of cardiovascular thrombotic events ( heart attacks and strokes ) in patients taking Celecoxib compared with those taking Rofecoxib.

FDA Bans Sale of Bextra Joint Ache Painkiller

Wed, 13 Apr 2005 00:00:00 -0700

The Food and Drug Administration has followed the US FDA's lead by banning the sale of Bextra, a kind of painkiller for joint aches which puts users at risk of heart attack and skin conditions.

The US FDA on April 7 asked Pfizer to withdraw Bextra from the market and announced actions to be taken regarding the marketing of NSAIDs (non-steroidal anti-inflammatory drugs).

FDA secretary-general Pakdi Pothisiri said the FDA had sought approval from the public health minister to ban the sale of Bextra in Thailand, and asked importer Pfizer (Thailand) Co to withdraw the drug.

All hospitals and provincial public health offices nationwide have been told to stop prescribing the drug.

The move came after the FDA's side-effects follow-up centre learned that the US FDA had found that Bextra, a non-steroidal anti-inflammatory drug under the COX-2 inhibitor drug group for joint complaints, posed risks of heart attack and skin diseases.

Pfizer has agreed to withdraw the medicine from the market, Mr Pakdi said.

The FDA would decide whether to revoke Bextra's production licence after consulting the pharmaceutical committee and considering further information from the US and European FDAs.

In Thailand, Bextra has been available only at hospitals.

Parker & Waichman, LLP Urges Current and Former Bextra and Celebrex Users to Explore Legal Options; Firm Continues to Investigate Cases Involving Serious and Fatal Side Effects

Tue, 12 Apr 2005 00:00:00 -0700

Parker & Waichman, LLP (http://www.yourlawyer.com) has been contacted by numerous current and former Bextra users who believe they were injured as a result of using the drug. Parker & Waichman, LLP continues to evaluate cases and consult with prospective clients who have experienced heart attacks and strokes as well as those who have been diagnosed with Stevens Johnson Syndrome and Toxic Epidermal Necrolysis during the use of Bextra. Bextra is a COX-2 arthritis pain reliever manufactured by Pfizer, Inc. (NYSE:PFE - News) that was removed from the market on April 7, 2005.

Parker & Waichman, LLP and Seeger Weiss LLP filed the first lawsuit in the United States in 2004 against Pfizer claiming their clients sustained injuries and resulting death as a result of ingestion of the drug Bextra.

Parker & Waichman, LLP has also received a significant amount of inquiries from patients who suffered heart attacks and strokes while using Celebrex. Both Bextra and Celebrex patients can receive a free case evaluation by visiting http://www.bextralegalhelp.com and http://www.celebrexlawyernetwork.com.

Based on the number of Celebrex inquiries and the research data available, Parker & Waichman, LLP supports Public Citizen's view that Celebrex should also be removed from the market. Parker & Waichman, LLP believes that the failure to remove Celebrex from the market puts millions of people at an unnecessary risk.

An unpublished study finished in 2000 indicated increased cardiac risks associated with Celebrex. A more recent study sponsored by the National Cancer Institute discovered that Celebrex's risk of causing a major cardiovascular event was two-and-a-half times greater than that for people taking a placebo. In 2004, almost twice as many prescriptions were written for Celebrex as for Bextra -- 23.9 million prescriptions compared to 12.9 million.

``The removal of Bextra is a step in the right direction but we cannot ignore the high rate of serious side effects associated with Celebrex,'' commented Jerrold S. Parker, one of the founding partners of Parker & Waichman, LLP. ``We continue to believe that Celebrex is a dangerous drug that is no more effective in treating pain and no better tolerated than traditional NSAIDS. We will continue to represent victims of all COX-2 drugs whose lives have been impaired or lost.'' For more information on Celebrex, please visit http://www.yourlawyer.com/practice/overview.htm?topic=Celebrex. For more information on Bextra please http://www.yourlawyer.com/practice/overview.htm?topic=Bextra

For more information on Parker & Waichman, LLP please visit: (http://www.yourlawyer.com) or call 1-800-LAW-INFO (1-800-529-4636). For more information on Public Citizen please visit http://www.worstpills.org.

Contact:

Parker & Waichman, LLP
David Krangle, Esq.
(800) LAW-INFO (800-529-4636) (toll free)
dkrangle@yourlawyer.com
www.yourlawyer.com

Pfizer Pulls Bextra From UAE

Tue, 12 Apr 2005 00:00:00 -0700

Pfizer has decided to also follow the US Food and Drug Administration ruling in the United Arab Emirates and withdraw its painkiller Bextra.

The company still hopes that the drug may be re-introduced but the FDA said its risks to the heart and stomach outweighed potential benefits.

IMB Statement on Bextra

Mon, 11 Apr 2005 00:00:00 -0700

The Irish Medicines Board has said it is advising doctors not to commence any new patients on the painkiller Bextra and is asking doctors to review patients already being treated with the drug with a view to changing their treatment.

The IMB says patients being treated with Bextra are advised to make an appointment with their doctor to discuss changing their current treatment.

Bextra's manufacturers, Pfizer, announced the withdrawal of the drug in recent days following concerns over reported side effects of serious skin reactions.

Some drugs in the class of drug to which Bextra belongs, Cox-2 inhibitors, has recently been associated with cardiac side effects, and another Cox-2 drug, Vioxx, was withdrawn from the market due to cardiac problems last year.

The IMN says its advice to doctors is being taken as a precautionary measure pending the finalisation of the assessment of the risk/benefit profile of Bextra, which is to be completed in around 10 days.

Pfizer decided to suspend the product after regulators in the United States expressed concern about the risk of serious skin reactions. The company said it had agreed to suspend sales in the US and Europe pending further discussions with the US regulatory authority, the FDA.

The IMB says the usage numbers of Bextra are considered low in Ireland, with about 3,000 patients currently being treated with the drug.

It says there is a range of other non-steroidal anti-inflammatory medicines available in the marketplace.

The IMB said the appropriateness of treatment can only be based on the doctor's assessment of the patient's medical history and current medical condition.

It says it is taking part in a EU-wide review of Bextra through its membership of the European Agency for the Evaluation of Medicinal Products (EMEA).

Pfizer New Zealand Bextra Advisory

Mon, 11 Apr 2005 00:00:00 -0700

Pfizer New Zealand will voluntarily suspend the marketing and distribution of Bextra and withdraw the product to pharmacy level, following a request from the regulator Medsafe.

Pfizer New Zealand general Manager Mark Crotty said Medsafe requested the voluntary suspension following similar actions in the US and EU, to allow further review of the overall benefit: risk of Bextra. Pfizer New Zealand is complying with this request to ensure consistency with other markets.

"After discussions with Medsafe, we are advising patients to seek a non-urgent appointment with their doctor to discuss stopping treatment of Bextra"

"This is not a recall to patient level."

Last week the US FDA informed Pfizer Inc that, in the agencys view, Bextras cardiovascular risk could not be differentiated from other NSAIDs. The agency has concluded that the additional increased risk of rare but serious skin reactions (SCAR) associated with Bextra, already described in its label, warrants its withdrawal.

Pfizer Inc respectfully disagrees with the FDAs position regarding the overall risk/benefit of Bextra, however, in deference to the agencys views the company agreed to suspend sales of the medicine in the USA pending further discussions with the FDA.

Bextra is available in New Zealand for the treatment of the signs and symptoms of osteoarthritis and rheumatoid arthritis, and was taken by approximately 1500 patients prior to the initiation of the review of the COX-2 inhibitor class in December 2004. There is currently precautionary advice in the prescribing information and consumer medicine information regarding the risk of developing serious cutaneous adverse reactions when taking Bextra.

Pfizer Suspends Sale of Bextra

Sat, 09 Apr 2005 00:00:00 -0700

The sale of painkiller Bextra, which has been suspended in Europe and the United States due to concerns that it causes serious skin reactions, has been suspended in Malaysia.

The drug, which is used to treat acute pain, primary dysmenorrhoea, rheumatoid arthritis and osteoarthritis, was launched here in April last year.

The United States Food and Drug Administration (FDA) had on Thursday asked Pfizer Inc, the manufacturer of the drug, to voluntarily remove Bextra from the market following reports of serious and potentially life-threatening skin reactions, including deaths, in patients.

"The risk of these reactions in individual patients is unpredictable, occurring in patients with and without a prior history of sulfa (a chemical substance in antibiotics) allergy and after both short- and long-term use," the FDA said on its website.

Another reason for the removal of the drug was the lack of adequate data on the cardiovascular safety of long-term users of the drug.

Pfizer Malaysia said yesterday that it had voluntarily suspended the sale of Bextra with immediate effect, in line with the FDAs recommendations, and after consulting with the Health Ministry.

"FDA had informed Pfizer that Bextra's cardiovascular risk could not be differentiated from other non-steroidal anti-inflammatory drugs (NSAIDs).

"In deference to the FDA's views, Pfizer Inc has agreed to suspend sales of Bextra pending further discussions with it.

"Patients using Bextra are advised to contact their doctors regarding discontinuing its use and seeking alternative treatment," the company said in a statement issued yesterday.

The FDA had also asked manufacturers of all marketed prescriptions of NSAIDs, including Celebrex, to include a boxed warning highlighting the potential risks of cardiovascular and gastrointestinal bleeding associated with its use.

Last September, the anti-inflammatory drug Vioxx was voluntary withdrawn from the Malaysian market by its manufacturer Merck after it was found to have doubled the risk of heart disease and stroke.

Bextra Is Pulled Off Market

Fri, 08 Apr 2005 00:00:00 -0700

Tens of millions of users of Motrin, Aleve, Celebrex and other painkillers should be given more information about their risks, such as heart attacks or ulcers, the Food and Drug Administration said yesterday.

In a sweeping safety action, regulators in the United States and Europe also asked Pfizer Inc. to withdraw its prescription pain reliever Bextra, saying it could do more harm than good compared with other drugs.

The FDA's actions on both prescription and nonprescription drugs sent its strongest sign yet of a change in agency tone on safety. It began from a controversy over one drug, Vioxx, which Merck & Co. Inc. voluntarily withdrew in September.

The failure of Vioxx rattled the industry, raised questions about the FDA itself, and sent millions of patients scrambling for different medications.

That, in turn, led to safety questions about other drugs, some of which, such as ibuprofen, have been used for decades in a business worth hundreds of billions of dollars.

Bextra's withdrawal also could spawn a wave of product-liability cases involving the drug, long criticized by some health advocates.

"Finally, it's buried. And that's a good thing," said Eric Topol, a researcher at the Cleveland Clinic Foundation and a Vioxx critic.

"Today's actions protect and advance the health of the millions of Americans who rely on these drugs every day," Steven K. Galson, acting director of the FDA's Center for Drug Evaluation and Research, said in a statement.

The FDA lists nearly 50 drugs or drug combinations as "nonsteroidal anti-inflammatory drugs," or NSAIDs, including the prescription drugs Celebrex and Bextra.

The over-the-counter, or nonprescription, drugs include Motrin and Advil (both ibuprofens), Aleve (naproxen), Mobic and Diclofenac.

Excluded from the list are aspirin and acetaminophen, also known as Tylenol.

"The FDA is asking the manufacturers of all over-the-counter NSAIDs to revise their labels to include more specific information about the potential cardiovascular and gastrointestinal risks," the FDA statement said, adding that skin reactions were also a risk.

The FDA did not spell out the basis for its concerns about the drugs yesterday. It also was vague on the specific wording of the warnings, saying only that they would differ depending on whether the drug is sold by prescription or over the counter.

"We plan to develop our proposed text for the new labeling in the next few weeks, and will request that each sponsor adopt that text," said John Jenkins, an official in the FDA's Office of New Drugs.

Some experts, while expressing skepticism about the impact of labels, praised the FDA's new stance on drug safety.

"It may be helpful if it gets people's attention not to exceed the over-the-counter dose," said Alastair J.J. Wood, a professor at Vanderbilt University Medical School and chairman of the FDA's arthritis panel.

Reaction was mixed among customers at a CVS store on Chestnut Street in Center City.

"I would still take them, even with a warning," said Linda Tripp, 59, of West Philadelphia, who said she used Advil for knee pain. "They have given me two and a half to three hours of slow relief."

But Tanya Thompson, 52, of North Philadelphia, said she read the labels and tried to heed them. "Let them put warnings on everything," Thompson said. "It's up to the consumer to decide whether to use it."

The FDA took the action almost seven weeks after its own panel of advisers recommended that the prescription drugs Bextra, Celebrex and Vioxx all known as Cox-2 inhibitors were safe enough to remain on the market.

However, the panel's vote had been close on Bextra and Vioxx, leading to speculation that the FDA might rule against them.

"This didn't surprise me a bit, and I'm a bit relieved," said Wood, who had voted against letting Bextra stay on, and Vioxx return to, the market.

All three drugs were designed to relieve pain without the older drugs' risks of gastrointestinal side effects, such as ulcers and internal bleeding. However, studies have found that the newer drugs carry higher risk of heart attack or strokes, or kidney and skin problems.

The FDA said it had asked Pfizer on Wednesday evening to cease selling Bextra after it concluded that the drug's risk of heart and skin reactions exceeded its benefits compared with other drugs on the market.

"Patients currently taking Bextra should contact their physicians to consider alternative treatments," the FDA said in a statement yesterday.

Hours later, European regulators contacted Pfizer and asked it to suspend sales of Bextra in the 25-nation European Union, according to Pfizer. It was unclear whether the FDA and European Union had coordinated their actions.

In its statement, Pfizer disputed the regulators' logic but said that, "in deference to the agency's views, the company has agreed to suspend sales of the medicine pending further discussions with the FDA."

Bextra was Pfizer's seventh-best-selling drug last year, with sales of $1.24 billion, but its sales have fallen.

The FDA let Pfizer keep Celebrex on the market but asked it to include more safety data about heart and stroke risks and insert a detailed Medication Guide for physicians.

Pfizer readily agreed and said it would "add expanded risk information."

Celebrex was Pfizer's No. 3-selling drug, with $2.78 billion in sales last year. But despite Pfizer's efforts to shield it from Vioxx-related fears, Celebrex sales have plunged.

Sidney M. Wolfe, director of health research at the advocacy group Public Citizen, faulted the FDA for not going far enough. "While we are pleased that the FDA has taken Bextra off the market, it has recklessly allowed Celebrex to continue to be sold."

Consumers Union also called for more action. "Removal of a dangerous drug from the market is a good thing, but it leads to the larger question: Why were these unsafe drugs being sold in the first place?" said Jeannine Kenney, senior policy analyst. "The FDA badly needs reform of its reactive, passive drug-safety system."

The FDA said no decision had been made yet on relaunching Vioxx, an option Merck raised during the advisory meeting. The agency said it would "carefully review" any new Merck application.

Merck said in its statement that it "respects the FDA decision" on Bextra and "looks forward to discussions with the FDA."

"Clearly, they want to take a second look, very careful look," at Vioxx before letting it back on the market, said Louis Morris, a former FDA official and now an industry consultant, who also was on the FDA panel.

Several experts said the Bextra withdrawal boded ill for Vioxx's return. "The hurdles are so high now. There's no chance," Wood said.

HSA Suspends Sales of Pfizer's Bextra in Singapore

Fri, 08 Apr 2005 00:00:00 -0700

Singapore has suspended the sales of Bextra, an anti-inflammatory drug produced by the global pharmaceutical manufacturer Pfizer.

Study shows that taking Bextra may pose risk to patients' cardiovascular safety or incur rare but serious skin reactions, which have led to similar bans on the drug in the United States, the European Union and Canada.

The Health Sciences Authority (HSA) of Singapore confirmed thatno local case of serious skin reactions had been reported, but it advised patients taking the drug to consult their doctors for alternative treatments.

Commonly used to treat osteoarthritis or rheumatoid arthritis, Bextra has entered Singapore market since May 2003 to deal with acute pain, the report said. Enditem

Bextra Taken Off Market After FDA Warns of Risks

Fri, 08 Apr 2005 00:00:00 -0700

Pfizer Inc. reluctantly halted sales of its arthritis painkiller Bextra on Thursday after the Food and Drug Administration concluded that it posed too many serious safety risks. It was the second major arthritis medication to be withdrawn in the last six months.

In addition to asking Pfizer to stop selling its $1.4 billion-a-year blockbuster, the FDA concluded that the entire class of anti-inflammatory painkillers carries a potentially increased risk of heart attack and stroke and it told manufacturers to substantially toughen the safety warnings on almost all nonnarcotic painkillers still on the market.

Prescription painkillers such as Celebrex and Mobic will remain available, but with the strongest safety warnings the FDA can require. The makers of nonprescription pain relievers such as Motrin and Aleve will be required to tell consumers more about their risks warning them to take the pills only for the short periods recommended on the labels, usually no more than two weeks.

For millions of pain sufferers, especially people with chronic arthritis, the FDA action was the latest twist in six months of misfortune that began with Merck & Co.'s withdrawal of the popular painkiller Vioxx. Drugs such as Vioxx, Celebrex and Bextra, hailed not long ago as near-miracle therapies, are now either gone or under a cloud, along with dozens of other anti-inflammatory drugs.

"Today's actions protect and advance the health of the millions of Americans who rely on these drugs every day," Steven Galson, acting director of FDA's Center for Drug Evaluation and Research, said in a statement. "FDA is providing the public information based on the latest available scientific data to guide the careful and appropriate use of these drugs."

Thursday's actions were among the most sweeping ever initiated by the FDA, which has traditionally been reluctant to take drugs off the market and cautious about branding an entire class of drugs as worrisome.

The FDA went beyond the recommendations of a 32-member panel of expert advisers that it brought together in February for a three-day public hearing about all nonnarcotic painkillers. That panel narrowly recommended that Bextra should be allowed to remain available and that Vioxx should be allowed back on the market under certain conditions. Galson said that because the expert panel's votes were so close, the agency believed that its actions are consistent with the recommendations.

Alastair Wood of Vanderbilt University, chairman of that committee, applauded the FDA Thursday for "asserting itself and taking a strong stand."

"When a bare minority votes to keep a drug on the market, that's not a safety endorsement - it's a devastating indictment," Wood said. "The FDA saw that and responded."

By taking Bextra off the market and requiring serious warnings on all other medications in the class known as non-steroidal anti-inflammatory drugs, or NSAIDs, the agency will significantly affect the lives of tens of millions of patients in pain who use them.

Bextra: More Risks Than Benefits

Fri, 08 Apr 2005 00:00:00 -0700

The Food and Drug Administration has asked pharmaceutical company Pfizer to pull Bextra off the market because of evidence that it increases the risk of heart attacks, strokes and a potentially fatal skin condition as well.

The Early Show medical correspondent Dr. Emily Senay explains what this might mean to you.

Bextra falls into a class of painkillers known as Cox-2 inhibtors that are very popular among people with arthritis. They have been in the news a lot lately (since the fall, in fact) when one of them, Vioxx, was voluntarily pulled of the market because people who took it were found to be at an increased risk of heart attack and stroke.

The FDA now says that Bextra poses these same heart risks and, in addition, people taking the drug are at risk for a serious and sometimes fatal skin reaction.

So what should patients taking Bextra do?

Pfizer, which makes Bextra, suggests that anybody on the drug stop taking it and contact their physician about other treatment options.

The FDA now wants all the drugs in this class that are still on the market to carry what's known as a "black box warning," which states clearly that these Cox-2 inhibitors can increase your chances of cardiovascular problems.

Merck, which manufactures Vioxx, stands by the decision to voluntarily remove the drug from the market. However, the company maintains that Vioxx offers unique benefits among the Cox-2 class of drugs.

So how is it that Celebrex (another very popular Cox-2) is still on the market? In February, a panel that advises the FDA said that Celebrex seemed to have the fewest cardiovascular side effects of all the Cox-2 drugs. But, as mentioned earlier, the government now wants it to carry one of those black box warning labels.

Over-the counter pain relievers such as Advil and Aleve, still very popular with arthritis sufferers, are not Cox-2 inhibitors. But the FDA has asked the makers of these medications to revise their labels to say that people who take them are at an increased risk for heart attacks, stroke, gastrointestinal bleeding and serious skin reactions.

The FDA says the the warning labels which will be placed on the over-the counter pain relievers will not be placed on aspirin because it has "special benefits when taken in low doses."

Another Drug For Pain Off Market

Fri, 08 Apr 2005 00:00:00 -0700

The Food and Drug Administration announced Thursday that Pfizer has agreed to stop selling Bextra, a popular arthritis drug, because its risks outweigh its benefits.

The FDA also will now require a "black box" warning the strongest warning on the labels of Pfizer's blockbuster arthritis drug, Celebrex, and other, older prescription anti-inflammatory pain relievers such as ibuprofen and naproxen. The warning will highlight the drugs' risks of heart attacks, strokes and bleeding of the digestive tract.

Over-the-counter anti-inflammatory pain relievers will have to add similar information to their labels, as well as a warning about rare, potentially fatal skin reactions, which the prescription drugs' labels already carry.

The halting of Bextra sales is just the latest blow to COX-2 inhibitor drugs. A decade ago, the drugs were touted as "super aspirins" because it was thought they could relieve pain and inflammation while unlike aspirin leaving the stomach lining intact.

Of all the anti-inflammatory pain-relievers, Bextra has been the one most commonly cited in reports of severe skin reactions, Steven Galson, acting director of the FDA's Center for Drug Evaluation and Research, said at a news conference.

The FDA asked Pfizer to stop selling Bextra because "it had no unique benefit, and it had the unique risk: the skin reaction," John Jenkins, director of the FDA's Office of New Drugs, said during the briefing. Galson said Celebrex is still on the market because the drug has a "positive risk/benefit balance."

At the request of European regulators, Pfizer said, it is also suspending sales of Bextra in the European Union. About 7 million people worldwide have taken Bextra since it was launched in 2001, Pfizer spokeswoman Susan Bro said. And 28 million worldwide have taken Celebrex since its launch in 2000, Bro said.

Since concerns over cardiovascular safety spurred Merck to pull its arthritis drug Vioxx off the market Sept. 30, "the FDA has been engaged in a re-evaluation of this class of drugs," Galson said.

In February, an FDA advisory panel unanimously concluded that Bextra, Vioxx and Celebrex, all COX-2 inhibitors, significantly raise heart and stroke risk. Nonetheless, a majority voted for keeping them on the market with restrictions. With Celebrex, the vote was 31-1 in favor of continued sales. But the panelists were nearly evenly split on whether Bextra or Vioxx should be on the market.

"Pfizer respectfully disagrees with FDA's position regarding the overall risk/benefit profile of Bextra," the company said in a statement. "For now, patients should stop taking Bextra and contact their physicians about appropriate treatment options." Pfizer said it would discuss with the FDA how the company might resume selling Bextra.

Curt Furberg, who voted against Bextra and Vioxx at the February meeting, called the FDA's announcement about Bextra "a victory for public health."

"I did not expect them to have the guts to do it," said Furberg, a medical epidemiologist at the Wake Forest University School of Medicine in North Carolina. "I feel vindicated."

Ban on Pfizer's Bextra Extends Beyond U.S.

Fri, 08 Apr 2005 00:00:00 -0700

Hong Kong suspended the sale of the painkiller Bextra on Friday one day after the drug was pulled off U.S. shelves because it has been linked to increased risk of heart attacks and a rare skin condition.

Patients should "stop taking Bextra and contact their physicians about appropriate treatment options," Hong Kong's Health Department said in a news release.

The drug's importer, Pfizer Corporation Hong Kong Ltd., has agreed to immediately stop selling the prescription medication, the department said.

Pfizer Inc. (PFE) suspended sales of Bextra in the U.S. on Thursday at the request of the U.S. Food and Drug Administration. The company said that the FDA cited a risk of serious skin reactions to Bextra.

FDA Tells Pfizer To Pull Bextra Off Market

Thu, 07 Apr 2005 00:00:00 -0700

Food and Drug Administration officials Thursday told Pfizer Inc. to take its COX-2 drug Bextra off the U.S. market and put a warning on Celebrex.

The FDA, based on recommendations from its Arthritis and Drug Safety and Risk Management Advisory Committee following a hearing in February, also asked manufacturers of all other prescription non-steroidal anti-inflammatory drugs to revise their labels to include the same box warning included on Celebrex.

Drugmakers selling NSAIDs also will have to include a medication guide for patients advising them of the potential for adverse events such as heart attack, stroke and gastrointestinal bleeding associated with this class of drugs.

Manufacturers of over-the-counter NSAIDs were asked to include more specific information about potential side effects, including a warning about potential skin reactions.

FDA began to investigate the COX-2 drugs last fall, and then included all NSAIDs, following studies that showed Merck's Vioxx, a COX-2 arthritis drug, doubled a patient's risk of heart attack when taken longer than 18 months.

Bextra Ban a Good Step, But FDA Should Pull Celebrex Too

Thu, 07 Apr 2005 00:00:00 -0700

In January, Public Citizen petitioned to have Bextra and Celebrex, two COX-2 inhibitors, removed from the market because they increase the risk of heart attacks. Today, the U.S. Food and Drug Administration (FDA) has called on Pfizer to pull Bextra from the shelves and place a warning on Celebrex.

While we are pleased that the FDA has taken Bextra off the market, it has recklessly allowed Celebrex to continue to be sold. An unpublished study finished in 2000 indicated increased cardiac risks associated with Celebrex.

Last year, almost twice as many prescriptions were written for Celebrex as for Bextra, 23.9 million prescriptions compared to 12.9 million. Neither Bextra nor Celebrex protects the gastrointestinal tract as drugmakers claim. Given that neither drug has any unique benefits but both carry unique cardiac risks, it is unconscionable to leave Celebrex on the market.

In addition, the FDA is sowing dangerous confusion by requiring all nonsteroidal anti-inflammatory drugs (NSAIDs) Celebrex and all non-aspirin NSAIDs to warn about increased cardiac risks, even though the risks of Celebrex are clearly higher than at least one NSAID, naproxen.

The FDA said today that it took its actions "based on the available scientific data, including data accumulated since the drugs were approved." But the agencys job is to ensure that drugs with risks that outweigh the benefits are taken off the market. We call on Congress, which is finally delving into FDAs operations, to investigate why the agency is not also pulling the equally dangerous Celebrex from the shelves.

Note: Bextra is the tenth prescription drug to be taken off the market in the past seven years that Public Citizen had previously warned consumers not to use. For four of the drugs: Vioxx, Baycol, Rezulin and Serzone; Public Citizen issued warnings more than two years before their removal from the market. In April 2001, Public Citizen warned patients not to use Celebrex

Health Canada Has Asked Pfizer to Suspend Sales of Its Drug Bextra and Informs Canadians of New Restrictions On The Use of Celebrex

Thu, 07 Apr 2005 00:00:00 -0700

Health Canada has asked Pfizer Canada to voluntarily discontinue sales of its drug Bextra in Canada until safety issues have been resolved. Pfizer has agreed and will be discontinuing sales.

Health Canada has asked the manufacturer to submit evidence to establish the safety of this drug product under the conditions of use for which it is recommended. In addition the manufacturer has been asked to provide Health Canada with a risk/benefit analysis indicating the product's unique therapeutic advantage.

Health Canada's decision is based on an ongoing review of information with regard to serious, potentially life-threatening skin reactions. It is based on Canadian and foreign data, including publicly available information from the United States. Health Canada has already published, on December 10, 2004 a public advisory indicating that serious potentially life threatening skin reactions had been reported in patients taking Bextra. The prescribing information and patient instructions were modified at that time to reflect the higher incidence of these events.

We encourage people taking Bextra to contact their physician to discuss discontinuing use and alternative treatments. After having consulted with a physician, consumers should return the product to their pharmacy. In order to avoid contaminating ground or municipal water systems, the product should not be flushed down the toilet or sink.

In addition to this action on Bextra Health Canada is also recommending important new usage restrictions for Celebrex(celecoxib), another selective COX-2 inhibitor.

The usage restrictions on Celebrex are based on Health Canada's ongoing scientific review of the cardiovascular safety of selective COX-2 inhibitor non-steroidal anti-inflammatory drugs (NSAIDs). Products such as Celebrex and Bextra work by selectively blocking an enzyme commonly known as COX-2 that is linked to pain, inflammation and fever.

Health Canada's ongoing scientific review started in the fall of 2004, when the long-term use of a similar drug, Vioxx(rofecoxib), was linked to an increased risk of heart attack and stroke, and its manufacturer withdrew it from the global market.

New restrictions concerning the use of Celebrex are as follows:

Patients who have had a heart attack or stroke, experienced serious chest pain related to heart disease, or who have had serious diseases of the heart such as congestive heart failure, should NOT use this medication.

Patients who have significant risk factors for heart attack or stroke should be aware that using this drug may increase this risk. Risk factors for heart attack and stroke include high blood pressure (treated or untreated), high cholesterol, diabetes and smoking. In consultation with their doctors, patients with such risk factors should consider using other types of medications or pain relief therapies.

This medication should be prescribed and used at the lowest possible dose, and for the shortest, necessary period of time.

Selective COX-2 inhibitor NSAIDs should only be used to treat the pain and inflammation of arthritis, and certain types of acute pain. These drugs may be used to treat osteoarthritis and rheumatoid arthritis. Celebrex may be used for the short-term (one week or less) management of moderate to severe pain in adults caused by conditions such as sprains, surgery or tooth extractions. In the past, Celebrex had been used to treat family polyposis (the presence of multiple polyps in the colon) but this indication was cancelled in December, 2004 and a public advisory was issued at that time.

Health Canada scientists continue to review Canadian and international safety data and other sources of information regarding cardiovascular risk and the use of other COX-2 inhibitor NSAIDs. They are also consulting external experts in fields such as cardiology, rheumatology and pharmacology. Health Canada will advise Canadians if other safety concerns arise.

Health Canada urges patients using Celebrex to consult their physicians in order to weigh the risks and benefits of these drugs in light of their own medical circumstances.

Pfizer Takes Painkiller Bextra Off Market

Thu, 07 Apr 2005 00:00:00 -0700

The painkiller Bextra was taken off the market Thursday, and the government wants similar prescription drugs to carry the strongest possible warnings about increased risk of heart attack and stroke among the millions of people who rely on them.

Pfizer Inc. suspended sales of Bextra in the United States and the European Union at the request of the Food and Drug Administration and European regulators. The company said that the FDA, in seeking Bextra's withdrawal, cited a risk of serious, sometimes fatal, skin reactions to Bextra on top of the risks shared by other similar drugs.

At issue are a broad class of painkillers known as nonsteroidal anti-inflammatory drugs, or NSAIDS. Bextra is a particular type of NSAID known as a Cox-2 inhibitor, a class of blockbuster sellers particularly popular among arthritis sufferers until a competitor Vioxx was pulled off the market last fall. That sparked questions about the safety of all similar drugs.

Pfizer's Celebrex can still sell, the FDA announced Thursday. But it, and all other prescription NSAIDS, must carry a black-box warning on its label that users may face an increased risk of cardiovascular side effects.

Scientists don't have enough information yet to tell if one of the remaining prescription painkillers is safer than another, FDA officials stressed. But, the agency decided that Bextra was more dangerous than its competitors because of the added skin side effect.

In addition to the prescription drugs, the FDA asked manufacturers of over-the-counter NSAID painkillers to revise their labels to clarify information about the risks of cardiovascular incidents, gastrointestinal bleeding and rare but serious skin reactions.

That doesn't mean the nonprescription drugs are dangerous, FDA officials stressed but the strengthened wording will make clear that patients should take those drugs only at the labeled dosage for short periods of time.

"People should not have a concern about continuing to take those products per those directions," said Dr. Steven Galson, acting director of FDA's Center for Drug Evaluation and Research.

For users of prescription-strength NSAIDS, the government said there was no reason to panic but that people should consult their physicians about which painkiller is best suited for them and to take the lowest effective dose.

"All these risks we're talking about have already been known," Galson stressed. "People should not worry about, from today to tomorrow, stopping the products."

Pfizer's advice to Bextra users: "For now, patients should stop taking Bextra and contact their physicians about appropriate treatment options."

Pfizer said it "respectfully disagrees" with FDA that Bextra was too risky to continue selling, and pledged further discussions with the agency about the possibility of returning it to the market.

Pfizer shares fell about 3 percent soon after Thursday's opening bell on the New York Stock Exchange.

In February, advisers to the FDA had recommended that people who depend on Celebrex, Bextra and Vioxx be allowed to continue to use them despite the health risks although it only narrowly backed Bextra. The panel said Vioxx posed the greatest heart risk and that Celebrex seemed have the fewest cardiovascular side effects among the Cox-2 drugs. It also recommended that the prescription drugs carry strong warnings, and that more study be done to better understand the drugs' risks.

Pfizer Halts Sales of Bextra

Thu, 07 Apr 2005 00:00:00 -0700

Pfizer has agreed to stop selling Bextra, a popular arthritis drug, the Food and Drug Administration announced Thursday, because the FDA believes its risks outweigh its benefits.

The FDA will also now require a black box warning the strongest type of warning on the labels of Pfizer's blockbuster arthritis drug, Celebrex, and other, older prescription anti-inflammatory pain-relievers, such as ibuprofen and naproxen. The warning will highlight the drugs' risks of heart attacks, strokes and digestive tract bleeding.

Over-the-counter pain relievers will have to add similar information to their labels, as well as a warning about rare, but potentially fatal skin reactions, which already is on the prescription drug labels.

The halting of Bextra sales is just the latest blow to COX-2 inhibitor drugs. A decade ago, COX-2 inhibitors had been touted as "super aspirins" because it was thought they could relieve pain and inflammation like aspirin while, unlike that drug, leaving the stomach intact.

Since cardiovascular safety concerns spurred Merck (MRK) to pull its blockbuster arthritis drug Vioxx off the market Sept. 30, "the FDA has been engaged in a re-evaluation of this class of drugs," Steven Galson, acting director of the FDA's Center for Drug Evaluation and Research, said at a press conference.

That process culminated in February with a three-day joint meeting of two FDA advisory committees, Galson said. Although panel members unanimously concluded that Bextra, Vioxx and Celebrex, all so-called COX-2 inhibitor drugs, significantly raise heart and stroke risk, a majority voted for keeping them on the market with restrictions to limit their use.

With Celebrex, the vote was 31-1 in favor of continued sales. But the panelists were nearly evenly split on whether Bextra or Vioxx should be on the market.

"Pfizer respectfully disagrees with FDA's position regarding the overall risk/benefit profile of Bextra," the company said in a statement. "For now, patients should stop taking Bextra and contact their physicians about appropriate treatment options."

In its statement, Pfizer said it would discuss with the FDA how the company might resume "making Bextra available to physicians and patients." The drug was approved by the FDA in November 2001.

It's not clear how suspension of Bextra sales might affect Vioxx's future. Merck executive Peter Kim surprised many at the advisory panel meeting when he suggested that Merck might resume marketing Vioxx if the advisory committee and the FDA conclude that the benefits of COX-2 inhibitors outweigh their risks.

"Merck respects the FDA's decision" on COX-2 inhibitors, the company said Thursday in a statement. "We look forward to discussions with the FDA."

Curt Furberg, who voted against Bextra and Vioxx at the February meeting and has published research about Bextra's cardiovascular risks, called FDA's announcement about Bextra "a victory for public health."

"I did not expect them to have the guts to do it," said Furberg, a medical epidemiologist at the Wake Forest University School of Medicine in Winston-Salem, N.C. "I feel vindicated."

Bextra Pulled Off Shelves

Thu, 07 Apr 2005 00:00:00 -0700

PHILLIPS: Well, important medical news to tell you about now. The drugmaker Pfizer is pulling its popular arthritis painkiller Bextra off the market.

The move comes at the urging of the Food and Drug Administration, which is also recommending the strongest possible safety warning for Pfizer's other arthritis drug, Celebrex.

CNN medical correspondent Elizabeth Cohen here to talk about what she knows about these drugs and the fact that Bextra is being pulled off the shelf.

ELIZABETH COHEN, CNN MEDICAL CORRESPONDENT: That's right.

And this is sort of yet another painkiller that's gotten into trouble. Now, I'll read you what officially what the FDA said today. They said, the FDA has asked Pfizer to withdraw Bextra from the market because the overall risk-vs.-benefit profile for the drug is unfavorable. That is a fancy way of saying that it does more harm than good.

Specifically, the harm is the studies found that people taking Bextra were more likely to have a heart attack or stroke than those who didn't, also more likely to contract a potentially deadly skin disease. And so the FDA decided to ask Pfizer. Pfizer said that they disagreed with the FDA's analysis, but that they agreed they would take it off the market.

Now, this is a very popular drug. In fact, last year, there were 12.8 prescriptions written for Bextra. And that meant $1.2 billion in sales. So, what do you do if you're taking Bextra? I'm sure you're asking yourself, what do I do? And Pfizer says stop taking it and talk to your doctor about alternatives.

But, remember, including over-the-counter painkillers, also carry risks. Now, it's important to note that some people, in consultation with their doctors, will decide that they want to continue taking drugs like Celebrex, which now has to carry a big warning about cardiovascular risks, and will want to continue to take over-the- counter drugs, despite the FDA's warning about heart and stroke risks.

And, Kyra, the reason for that is that some people are in so much pain that they have trouble going about their day. And they and their doctors may say, you know what? I'm not at a very particularly high risk of having a heart attack or stroke. So, if it elevates my risk a little bit, that's OK, because these drugs help me make it through the day. Other people are going to make different situations. It's very individual.

PHILLIPS: Well, we see that a lot of people take Bextra or took Bextra. But I bet even more take over-the-counter painkillers. So, is it still OK to take other how do you know what's OK to take now and what's not?

COHEN: It's so confusing.

PHILLIPS: Yes.

COHEN: It's so confusing. We're going to give people a little advice here. What the Food and Drug Administration has to say about over-the-counter painkillers like Advil, Motrin, Aleve, that class of nonsteroidal anti-inflammatories is, only take the dose that is recommended on the label. Take these drugs for no longer than two weeks.

And, after two weeks, see your doctor. When people really ran into trouble with these drugs, for the most part, it was when they were taking dosages that were too high and when they were taking them for month after month or even year after year after year.

PHILLIPS: All right, Bextra is getting pulled, but Celebrex is saying, but Celebrex having to have this massive warning label now. Why not just pull that one also?

PHILLIPS: Right. It's called a black box warning. And the reason why it's called that is that it's in a big black box at the top of the label. So, it's very clear, cardiovascular risk, so that you know the risk you're taking.

We asked the FDA, why are you letting Celebrex stay on the market? And they said because this deadly skin disease seems to be more likely when you take Bextra. And they said, in fact, as of December, that four people had died when they were taking Bextra from this skin disorder. So, it was really the skin disorder being associated with Bextra. That's what really tipped the scales for the FDA.

Pfizer Pulls Bextra

Thu, 07 Apr 2005 00:00:00 -0700

First, though, there is important medical news that you need to know about. The drugmaker Pfizer is pulling its arthritis painkiller Bextra off the market. The Food and Drug Administration asked for the recall. The FDA also called for the strongest possible warning on Pfizer's other big arthritis painkiller, Celebrex.

Our medical correspondent Elizabeth Cohen standing by with important details.

Elizabeth, what's going on?

ELIZABETH COHEN, CNN MEDICAL CORRESPONDENT: Wolf, well the Food and Drug Administration has just had a press conference, and issued this statement. And in it they say the FDA has asked Pfizer to withdraw Bextra from the market because the overall risk versus the benefit profile for the drug is unfavorable.

Well, that's a fancy way of saying that when they looked at the data, Bextra did more harm than good. And the harm, specifically, is an increased risk of having a heart attack or stroke while taking Bextra, and also an increased risk of having a potentially life-threatening skin condition.

So, now, of course, the big question for Bextra users is, what do I do? Well, Pfizer says stop taking Bextra. Stop taking it and talk to your doctor, those are the instructions from Pfizer. And they also say, when you talk to your doctor about alternatives, remember that other painkillers also carry risks.

Wolf, you mentioned Celebrex, and the FDA has said that Celebrex now needs to carry it's called a black box warning. That's a warning in a big prominent black box that talks about the heart attack and stroke risk and also the increased risk of having gastrointestinal bleeding.

The sales for Bextra have been very high, of course won't be high much longer. 12.8 million prescriptions for Bextra were written in 2004. $1.2 billion in sales.

Now, Wolf, another thing that people need to remember is, if they're take Celebrex, or even if they're taking over-the-counter painkillers, which also carries some increased risk, for some people those risks are worth it. Some people are going to say, "My pain is so bad I can't really live my life the way I want to." And they and their doctor together might decide that it's worth them continuing to take these drugs Wolf.

BLITZER: What about the people who would take these painkillers, especially the over-the-counter painkillers? What are they supposed to do now?

COHEN: Right. Well, they also should talk to their doctor, and the should follow the Food and Drug Administration's advice. And that advice specifically is to take the dose that's recommend on the label. Take it for no longer than two weeks. If you want to take it for longer than two weeks, you need to talk to your doctor.

Wolf, the problems that the FDA found when people were taking over-the-counter drugs like Advil or Alleve, they tended to be when people took them for a long time and at high doses.

BLITZER: The FDA asked for Bextra to come off the market, but Celebrex still staying on the market. Why?

COHEN: What tipped the scales apparently, according to the FDA, is that Bextra seemed to have a more severe relationship with this life-threatening skin condition. In fact, in December, they said that four people had died because of this skin condition when they were taking Bextra.

So it was the skin condition, not the heart attack and stroke risk. The heart attack and stroke risk seems to be the same with Celebrex and Bexra, but the skin condition seems to be worse for people taking Bextra.

BLITZER: Elizabeth Cohen reporting for us important information, medical information. Thanks, Elizabeth, very much.

FDA Pulls Painkiller, Orders New Warnings on Others

Thu, 07 Apr 2005 00:00:00 -0700

In a sweeping move to address one of its worst drug safety debacles, the Food and Drug Administration announced Thursday that dozens of widely used prescription painkillers must now carry the government's strongest warning that they pose risks of heart attacks and strokes.

And one blockbuster painkiller, Bextra, was removed from the market. The FDA said it can cause potentially life-threatening skin reactions in some patients, as well as heart problems.

Bextra, along with Celebrex, have been medications of choice for millions of patients suffering from arthritis and other forms of chronic pain. The two drugs, known as COX-2 inhibitors, belong to a much larger category of medications called nonsteroidal anti-inflammatory drugs, or NSAIDs.

All prescription drugs classified as NSAIDs must now carry the stronger warning label.

In weaker, nonprescription forms such as Advil, Motrin and Aleve, NSAIDs are likely to be found in almost every household in America. The FDA emphasized that these nonprescription versions are safe. But it said they should be taken according to directions and only for limited periods of time.

In other action, the agency made it less likely that another COX-2 inhibitor taken off the market last fall Vioxx will become available again. The FDA said its maker, Merck, must submit a new application for approval and go before an expert advisory panel. It was Merck's decision to withdraw Vioxx that marked the beginning of cascading concerns about the painkillers.

The FDA's actions Thursday, which go beyond the steps proposed in February by its scientific advisory committee, suggest the embattled agency has decided to take a tougher approach to the problem of health risks that surface in drugs after they have been approved for market.

Thursday's action was one of the largest relabeling orders in FDA history.

In recent months, critics in Congress and elsewhere have subjected the agency to criticism for relying too much on drug makers to sound the alarm over potential safety threats that surface after drugs have reached the market and begun to be used by patients.

And the actions were at least partial vindication for agency whistle-blower Dr. David Graham, who had unsuccessfully tried last year to warn of problems with Vioxx. Graham testified in congressional hearings that Bextra should also be withdrawn from the market.

Graham has estimated that of the millions who took Vioxx for arthritis, back pain and other ailments, as many 139,000 Americans may have suffered heart attacks and strokes. Of those, 26,000 to 55,600 may have died, he suggested. The FDA disputes Graham's calculations and says the total number of fatalities is probably significantly lower, but it does not dispute the seriousness of the problem.

Signaling a more aggressive strategy, Dr. Steven Galson, acting director of the FDA's Center for Drug Evaluation and Research, said the public can expect further regulatory decisions and information alerts about the risks and benefits of painkillers.

"Let me emphasize now, this announcement is unlikely to be the last word you'll hear on these drugs," Galson told reporters on a conference call. "Clinical investigations continue. And in our new spirit of keeping the public informed earlier of emerging drug safety issues we may be providing further modifications as new information comes to light."

He said the FDA concluded that all prescription NSAID drugs, at least in theory, can increase the risk of heart attacks and strokes.

The tougher approach is in line with demands by congressional and other critics that the FDA become more aggressive in monitoring drugs it has approved for market.

"The FDA took a stand in support of public health," said Dr. Curt Furberg of Wake Forest University, who had criticized the agency's handling of safety concerns about Vioxx. "I think patients now can have some hope that the FDA in the future will be the guardian of drug safety."

Other experts suggested the agency's action could lead to confusion for patients and doctors, particularly since there is a dearth of hard data on the heart risks of most of the nonsteroidal anti-inflammatory drugs. For example, there is no way at present to know whether some of the drugs are safer than others.

"I am having a very difficult time managing my post-surgery patients," said Dr. Richard Vanis, an orthopedic surgeon in Arcadia, Calif. Vanis said he has been prescribing narcotic pain relievers for high-risk patients who would have been given Vioxx in the past. Some of the drugs are "horribly addicting," he said.

On Thursday, Vanis examined a 61-year-old patient with severe arthritis and heart disease who had run out of Vioxx. The patient refused to stop taking the pain reliever when it was recalled last fall.

"I don't know what I am going to do in his case," Vanis said.

The FDA said all prescription-strength forms of NSAIDS would now carry a so-called "black-box" warning, the strongest it can impose. The warnings will be printed in bold type and surrounded by a black box at the top of instructions provided to doctors.

Lower-strength over-the-counter versions of the traditional drugs will not carry such a dramatic warning, though patient information will be changed to include details about possible heart and stroke risks.

The FDA sought to reassure patients taking nonprescription painkillers that they face no excessive risks. "The over-the-counter products, when taken according to directions are not an issue, and people should not be concerned," the FDA's Galson said.

He also stressed that patients taking aspirin to reduce their risk of having a heart attack should continue to do so. "None of this applies to aspirin," Galson said. "It has special benefits when taken in low doses."

The FDA actions were a blow to Pfizer Inc., which makes Bextra and Celebrex, a far more popular prescription drug in the COX-2 family. Touted as a stomach-friendly alternative to aspirin and other drugs, COX-2 inhibitors were heavily advertised by drug companies.

Pfizer said it disagreed with the FDA's decision to withdraw the drug, but had deferred to the wishes of regulators. The company also agreed to conduct additional long-term studies of the benefits and risks of Celebrex.

More than 500 cases are pending against Merck from patients who claim they were harmed by Vioxx.

A congressional investigation last year revealed that the FDA had downplayed or ignored repeated warnings from its own drug safety reviewers and from academic scientists about the cardiovascular risks of Vioxx. That led lawmakers to call for the creation of a much stronger and more independent drug safety office within the agency.

The stronger warning label on Celebrex is expected to have the effect of sharply restricting its use. As for Vioxx, Dr. Alastair J.J. Wood of Vanderbilt University Medical Center, said, "It seems inconceivable to me that Merck would try to bring it back."

Wood chaired an expert advisory panel that met for three days earlier this year to hear testimony and weigh the risks and benefits of COX-2 drugs. The panel recommended that Vioxx, Celebrex and Bextra should be available on the market, albeit with black box warnings. Those recommendations led Merck to indicate it might try to bring Vioxx back.

That possibility dimmed as a result of Thursday's announcements, Wood was suggesting.

Graham, the FDA whistle-blower, said in an interview he was glad the FDA finally agreed with him. But he said the agency's warning on Celebrex did not go far enough.

"I'm disappointed they didn't ban the (high) 400-milligram dose of Celebrex," Graham said. "The benefit of the higher dose doesn't exceed the risk, and I would challenge the FDA to present evidence to the contrary."

Agency officials said they are urging patients on Celebrex to take the smallest possible dose for the shortest possible time.

The consumer advocacy group Public Citizen said the FDA should have taken Celebrex off the market as well.

Meantime, a study published in the Journal of Immunology found that COX-2 drugs may have other powerful side effects. Laboratory and animal tests showed the drugs may also suppress the immune system by affecting antibodies that attack invading germs.

Bextra Lawsuit Stevens Johnson Syndrome Heart Attack Side Effects Lawyer / Attorney

Thu, 07 Apr 2005 00:00:00 -0700

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On April 7, 2005, the FDA and European regulators formally asked Pfizer to suspend sales of Bextra in the United States and Europe. As a result, Pfizer announced it would halt sales of the drug in the United States and the European Union countries immediately. The FDA stated that the risks posed by Bextra outweigh its benefits. These risks include a high rate of heart attacks, strokes, other cardiovascular injuries and Stevens Johnson Syndrome.

FDA advisory committee hearings held in February 2005 examined whether Celebrex and Bextra offered enough benefits to stay on the market, if they needed stronger warnings and what further research was needed. The advisers met from February 16, 2005 through February 18, 2005 and ultimately voted to keep Bextra on the market. The New York Times reported that 10 of the 32 government drug advisers who voted to keep Bextra and the other COX-2 drugs on the market have consulted for pharmaceutical manufacturers. If these 10 advisers had not cast their votes, the committee would have voted 12 to 8 that Bextra should be withdrawn.

Bextra (generic name: valdecoxib), a Cox-2 Inhibitor drug, is in the same drug family as Vioxx, Celebrex and Naproxen. People prescribed Bextra have experienced a higher number of heart attacks, strokes and other cardiovascular problems. Bextra is prescribed for the treatment of adult rheumatoid arthritis, and the pain associated with menstrual cramping.

Bextra has also been linked to Stevens Johnson Syndrome and other skin hypersensitivity disorders. Stevens Johnson Syndrome is an extreme allergic reaction to chemicals. Common causes are the drugs including Arava (leflunomide), painkillers, and sulfa antibiotics. Bextra has now been linked to this potentially life threatening syndrome. Symptoms of Stevens Johnson Syndrome are blistering, fever, cough, malaise, swelling and lesions of gums, tongue, or lips, excessive tearing or "stickiness" of eyes, sores in the genital tract causing painful urination, skin rash, difficulty breathing. Patients who have severe allergies to antibiotics should not use Bextra.

Merck voluntarily withdrew Vioxx in September after a study showed the drug doubled the risk of heart attack and stroke in patients who took it for at least 18 months. Following the Vioxx recall, questions arose about the similar pain pills from Pfizer, Celebrex and Bextra, as well as non-prescription drugs such as Naproxen (Aleve). All pain drugs in the class known as Cox-2 Inhibitors increase the risk of heart attacks and strokes, a top scientist told a US regulatory panel. Dr. Garret Fitzgerald, a cox-2 expert and researcher at the University of Pennsylvania, said the body reacts in the same way to drugs including Merck's Vioxx and Pfizer's Celebrex and Bextra. Dr. Fitzgerald said the drugs create an imbalance in the body's cardiovascular system that leads to an increased risk of heart attacks and strokes.

If you or a loved one took Bextra and suffered side effects, please fill out the form at the right for a free lawsuit case evaluation by a qualified drug side effects attorney.