Natrecor label changed to show death risk

After two studies that clearly showed that the label Natrecor did not warn about the serious side effects of Natrecor, Johnson & Johnson, the manufacturer, has decided to change the label. Links to previous studies are below:

Natrecor increases risk of death

Natrecor damages kidney but no recall yet

The label change was approved last week by the Food and Drug Administration (FDA) and the information is now available on the company's website though no press release was issued to make consumers aware of the risks. The label shows a chart with data pooled from seven studies and the clear message is that 5.3% of people die when they took Natrecor compared to just 4.3% in a control group. However, the company argues that the data is not conclusive. It says on the insert, "There were few deaths in these studies, so the confidence limits around the hazard ratios for mortality are wide. The studies are also small, so some potentially important baseline imbalances exist among the treatment groups, the effects of which cannot be ascertained."

The label change does not necessarily amount to a warning and is definitely nowhere close to a drug recall.

Natrecor increases risk of death

After it was found that Natrecor may cause kidney damage, another study by Jonathan D. Sackner-Bernstein, MD; Marcin Kowalski, MD; Marshal Fox, MD; and Keith Aaronson, MD, MS shows that compared with noninotrope-based control therapy, nesiritide (or Natrecor) may be associated with an increased risk of death after treatment for acutely decompensated heart failure. The authors recommend that the possibility of an increased risk of death should be investigated in a large-scale, adequately powered, controlled trial before routine use of Natrecor for acutely decompensated heart failure.

The study has been published in the Journal of American Medical Association (JAMA). Nesiritide typically improves symptoms in patients with acutely decompensated heart failure compared with placebo and appears to be safer than dobutamine. Its short-term safety relative to standard diuretic and vasodilator therapies is less clear. The researchers decided to investigate the safety of Natrecor relative to noninotrope-based control therapies, primarily consisting of diuretics or vasodilators.

The data for the study came primarily from reports of completed clinical trials from the US Food and Drug Administration (FDA), the study sponsor (Scios Inc), a PubMed literature search using the terms nesiritide, clinical trials, and humans, and a manual search of annual meetings of 3 heart associations.

Biogen faces class action lawsuits in Tysabri recall case

After Tysabri recall announcement by Biogen and Elan, there have been several reports of insider trading by Biogen executives. In fact it is now being reported that the company management did not really have patient safety and drug development as their highest priorities. The company executives were simply more interested in pumping the stock and then getting out when the story unfolded.

No surprise then that shares of both companies are hurting. There are rumors that Elan may not even survive the controversy. And then come the class action lawsuits, along with a formal investigation by the United States Securities and Exchange Commission (SEC).

The latest lawsuit filed by Stull, Stull & Brody charges Biogen, William Rastetter, and James Mullen with violations of the Securities Exchange Act of 1934. More specifically, the Complaint alleges that the Company failed to disclose and misrepresented the following materially adverse facts which were known to defendants or recklessly disregarded by them:

1. That TYSABRI posed serious immunity-system side effects;
2. That TYSABRI, like other MS drugs, made patients susceptible to progressive multifocal leukoencephalopathy ("PML") by changing the way certain white blood cells function thereby allowing PML, a normally dormant virus, to run rampant within the human body;
3. That defendants knew and/or recklessly disregarded documented facts that MS drugs can cause greater incidents of PML to occur; and
4. That defendants concealed these facts in order to fast track TYSABRI for FDA approval so that they could reap the financial benefits from the sales of the drug.

On February 28, 2005, before the market opened, Biogen announced a voluntary suspension in the marketing of TYSABRI (natalizumab), a treatment for multiple sclerosis (MS) because of two serious adverse events that have occurred in patients treated with TYSABRI in combination with AVONEX) (Interferon beta-1a) in clinical trials. News of this shocked the market. Shares of Biogen fell $28.63 per share, or 42.44 percent, to close at $38.65 on unusually high trading volume.

Recommended article: Class action lawsuit filed against Biogen in Tysabri recall case

No Levitra recall despite misleading ads

Levitra, the drug that competes with Viagra, is in trouble, though there is no indication that it is in the kind of trouble like Vioxx, Celebrex, and Bextra are. In other words, no talk of a "Levitra recall" yet since that is the last word any drugmaker CEO wants to hear these days. The US Food & Drug Administration (FDA) is asking Bayer Pharmaceuticals Corporation (Bayer). Schering Corporation (Schering) and GlaxoSmithKline (GSK), which market Levitra on behalf of Bayer, that the Division of Drug Marketing, Advertising, and Communications (DDMAC) has reviewed a direct-to-consumer television advertisement (TV ad) for Levitra (vardenafil HCl) Tablets (Levitra) entitled "My Man" and found that the ad fails to disclose the drug's indication, fails to include information relating to the major side effects and contraindications, and fails to make adequate provision for dissemination of the FDA-approved labeling in violation of the Federal Food, Drug and Cosmetic Act (Act).

In a letter sent to the drugmakers, the FDA's Joan Hankin charges that the TV ad is misleading because it contains representations or suggestions that Levitra is superior to other erectile dysfunction treatments when this has not been demonstrated by substantial evidence or substantial clinical experience.

In the opinion of the FDA, the TV ad makes representations or suggestions that Levitra has a positive effect on the relationship between two intimate individuals, and that Levitra will provide a satisfying personal experience from the female partner's perspective. For example, the partner of the Levitra patient speaks to the camera while the video flashes-back to moments when she and her "man" appear romantically involved.

Another scene shows a smiling man and two other quick scenes depict the couple engaged in flirtatious behavior. In one of these scenes, the man strokes the woman's hair and face as she affectionately puts her hand on his wrist. In the other, she puts her arms around his neck and they embrace. The totality of the TV ad also represents or suggests that Levitra will provide a satisfying experience from the female partner's perspective. For example, the visual images in the ad show the female partner of the Levitra patient in moments where she appears to be romantically involved with the Levitra patient and the audio portion contains claims from the female partner about how Levitra is the "best way to experience the difference."

The fact that effectiveness claims are being made about Levitra in the TV ad is acknowledged by the sponsor by the inclusion of a qualifier to the claim "Levitra. When it counts" ­ a concurrent SUPER that states: "Individual results may vary." This disclosure about varying "results" recognizes that the ad makes representations about the drug's efficacy.

DDMAC has directed that Bayer immediately cease the dissemination of promotional materials for Levitra the same as or similar to those described above.

Related article

Viagra recall

Paxil class action lawsuit filed

The problems with Paxil CR are not over yet for the drugmaker GlaxoSmithKline. After a FDA imposed Paxil CR recall of certain batches of the drug at one of its plants, the company is still struggling to get back on the tracks. Now comes the news that the shareholders are filing class action lawsuits against the company.

Stull, Stull, Brody and Schatz & Nobel are the two law firms taking the lead in filing these lawsuits. The plaintiffs are the purchasers of the publicly traded securities of GlaxoSmithKline between February 21, 2001 and August 5, 2004, inclusive (the “Class Period”). The complaint alleges that GlaxoSmithKline violated federal securities laws by issuing false or misleading public statements. Specifically, the Complaint alleges that GlaxoSmithKline improperly concealed deficiencies with its selective serotonin reuptake inhibitor (“SSRI”) drug, Paxil, in treating adolescent depression. On August 5, 2004, the Wall Street Journal published an article that reported that a new analysis by the FDA had confirmed the link between SSRIs (including Paxil) and suicidal tendencies in young people.

Stull, Stull & Brody has litigated many class actions for violations of securities laws in federal courts over the past 30 years and has obtained court approval of substantial settlements on numerous occasions.

Related article: Celebrex recall

No recall yet for Zyprexa, Abilify, Seroquel, Risperdal, Clozaril, Geodon, Symbyax

The Food and Drug Administration (FDA) has issued a public health advisory to alert health care providers, patients, and patient caregivers to new safety information concerning an unapproved (i.e., “off-label”) use of certain drugs called “atypical antipsychotic drugs.” These drugs are approved for the treatment of schizophrenia and mania, but clinical studies of these drugs to treat behavioral disorders in elderly patients with dementia have shown a higher death rate associated with their use compared to patients receiving a placebo (sugar pill).

This advisory applies to such antipsychotic drugs as Abilify (aripiprazole), Zyprexa (olanzapine), Seroquel (quetiapine), Risperdal (risperidone), Clozaril (clozapine) and Geodon (ziprasidone). Symbyax, which is approved for treatment of depressive episodes associated with bipolar disorder is also included in the agency’s advisory.

FDA is requesting that the manufacturers of all of these kinds of drugs add a boxed warning to their drug labeling describing this risk and noting that these drugs are not approved for the treatment of behavioral symptoms in elderly patients with dementia. Patients receiving these drugs for treatment of behavioral disorders associated with dementia should have their treatment reviewed by their health care providers.

In analyses of seventeen placebo-controlled studies of four drugs in this class, the rate of death for those elderly patients with dementia was about 1.6 to 1.7 times that of placebo. Although the causes of death were varied, most seemed to be either heart-related (such as heart failure or sudden death) or from infections (pneumonia).

The atypical antipsychotics fall into three drug classes based on their chemical structure. Because the increase in mortality was seen with atypical antipsychotic medications in all three chemical classes, the agency has concluded that the effect is probably related to the common pharmacologic effects of all atypical antipsychotic medications, including those that have not been studied in the dementia population.

The agency is considering adding a warning to the labeling of older antipsychotic medications because limited data also suggest a similar increase in mortality for these drugs. The review of the data on these older drugs, however, is still on-going.

Related article: Zyprexa class action lawsuits

Razadyne is new name for Reminyl

To support safe prescribing and dispensing for patients with Alzheimer's disease, Ortho-McNeil Neurologics, Inc., announced today that REMINYL (galantamine hydrobromide) will now be marketed in the U.S. under the new product trade name RAZADYNE (galantamine hydrobromide). The extended release formulation of galantamine, approved in December 2004, will be marketed as RAZADYNE ER (galantamine hydrobromide). The products are indicated for the treatment of the symptoms of mild to moderate Alzheimer's disease.

Reminyl is manufactured by Johnson &Johnson. The drug has been mired in a controversy leading to speculation of a Reminyl recall. Investigations by health authorities are still in progress.

According to the firm, the name is being changed to help avoid confusion with the diabetes drug AMARYL (glimepiride), which is marketed by Sanofi-Aventis. Ortho-McNeil Neurologics, Inc., began working closely with the U.S. Food and Drug Administration (FDA) since learning of several reports of prescribing and dispensing errors between REMINYL and AMARYL.

"Our top priority is to ensure the well-being of our patients," said Joseph Hulihan, M.D., vice president, Medical Affairs, Ortho-McNeil Neurologics, Inc. "Through ongoing discussions with the FDA, we agreed that the best way to avoid future dispensing errors was to change the name of REMINYL which came onto the market nearly six years after AMARYL."

"Medication errors occur frequently among elderly patients, and the need for clarity in product names is particularly important for patients with Alzheimer's disease and their caregivers," said Stephen Aronson, M.D., clinical assistant professor, University of Michigan Medical School. "I believe this change is key to keeping safety at the forefront for my patients."

Approximately two million patients have been treated with REMINYL to date. According to reports submitted to the FDA and the U.S. Pharmacopoeia since REMINYL was introduced in the United States, a few prescriptions for REMINYL have been incorrectly written, interpreted, labeled or filled, leading to confusion between REMINYL and AMARYL. The accidental administration of AMARYL to patients with Alzheimer's disease who did not have diabetes mellitus resulted in serious events, including severe hypoglycemia and – in two cases – death.

The immediate release formulation bearing the new name, RAZADYNE, will be available in pharmacies beginning in July 2005. Prescriptions written before that time will be filled with REMINYL. Product bearing the new name, RAZADYNE ER, the extended release formulation, will be available in pharmacies beginning in mid-May 2005.  In clinical trials, the most frequent adverse events with RAZADYNE ER were similar to those seen with RAZADYNE. The most common side effects are nausea, vomiting, diarrhea, loss of appetite and weight loss. Typically, these side effects are mild and temporary. Some people experience a slowed heart rate, which may lead to fainting. Serious stomach problems can occur in people taking medications such as nonsteroidal anti-inflammatory drugs (NSAIDs) or those at risk for stomach ulcers.

Bextra recall makes FDA look incompetent

The recent Bextra recall news and prior to that the manner in which Vioxx recall was handled by the FDA has made the agency look incompetent in the eyes of the world. FDA's own scientist Dr David Graham has charged the agency with putting interests of drug firms ahead of the American people. No wonder FDA has become a topic of ridicule. And the ones to take the most advantage of the situation are Canadian drug pharmacies that have cropped up during recent years to sell cheap prescription drugs to Americans who can not afford the prohibitive prices in the US. (Related article: How to import prescription drugs from Canada?)

The pharmacies are attacking the argument that the FDA has made over the years that drugs from Canada may not be safe. It is the same argument that the drug companies offer but even six-year olds find it laughable but that has not stopped the Bush Administration or the FDA or the pharmaceutical firms from making it. As the drug firms and Canadian pharmacies fight these battles, some interesting observations are being made in Canada about the FDA and the drug companies. (Related article: American doctors support importing prescription drugs from Canada)

"We note with some dismay that Pfizer, which has vigorously worked to restrict the supply of safe prescriptions from outside the U.S. for American citizens, still does not recognize the potential safety problems with its Cox- 2 pain relievers, choosing to disagree with the FDA findings, and offering only to work to add 'expanded' information on its labeling. It is ironic that Pfizer has been quick to push the FDA to question the safety of even their own products from registered Canadian pharmacies, but is now challenging the ability of the very same organization to identify a known safety problem with other of its products," says Jeff Uhl, president and CEO of Universal Drugstore. (Related article: Bextra recall announced but Pfizer disagrees with the FDA)

"For five years now, we have been dispensing safe and affordable prescription medications to the uninsured and underinsured in the U.S. and all along we have had officials on both sides of the border, including the FDA, warning Americans not to order drugs from Canada because they may not be safe but are FDA approved drugs available in the United States safe," asks Daren Jorgenson of Canadameds. "There are millions of people in North America and around the world that are taking drugs such as Bextra and Celebrex for years but only now we are learning that they may pose serious risks to ones health? What purpose does the FDA serve and how can it claim that drugs from Canada may not be safe when FDA approved drugs such as Bextra, Vioxx and Celebrex are now being introduced as drugs that may pose a serious risk to ones health," continues Jorgenson.

Drug re-importation from Canada has become a major issue in the United States, and much has been stated and written about this industry in the media. The American public has been told on numerous occasions by the FDA, the drug manufacturers, and certain politicians, that drugs from Canada may not be safe and that the high prices of drugs in the U.S. are justified by research and development costs. There are millions of American seniors, many of whom order prescription drugs from pharmacies in Canada, that have spent a significant amount of their incomes taking FDA approved drugs that companies such as Pfizer deemed safe who are now left wondering. "I can't imagine how those individuals that have had to decide between food on the table and prescription drugs such as Bextra and Vioxx are now feeling knowing that the thousands that they have spent on prescription drugs may have actually done more harm than good. Next time anyone from the FDA tells you that drugs from Canada may not be safe and next time the drug companies try to justify the high prices of prescriptions drugs with R&D costs, I ask the millions of suffering Americans in the United States to consider how accurate these statements actually are, realizing that some of the worlds most consumed drugs, which were FDA approved, are now being deemed a health risk," says Jorgenson.

John Lehmann, a pharmacologist, who is expected to provide expert testimony at some Vioxx hearings, explains that the FDA is simply repeating what the drug firms are tellint it to say. He says, "There's a nod and a wink between the industry and the FDA in this case and others."

Recommended article: Truth about the FDA and prescription drugs

Drug combination options for Vioxx, Bextra patients

In the midst of the recent controversy and confusion over serious side effects from pain medications, a new UCLA and Veterans Affairs Greater Los Angeles Healthcare System study demonstrates that for arthritis sufferers at high risk for gastrointestinal problems who traditionally may have used a drug like Vioxx, the most cost-effective and safest treatment is actually a common painkiller combined with an acid-reducing drug. This discussion has become particularly relevant after Bextra recall and a black-box warning on Celebrex.

According to an article published in the medical journal Arthritis Care and Research, the study used a sophisticated economic model to develop patient scenarios and compare costs of the following three therapies often used for treating pain from chronic arthritis:

1. A nonsteroidal anti-inflammatory drug alone, such as Naproxen or Ibuprofen;
2. A nonsteroidal anti-inflammatory drug combined with an acid-reducing drug (proton pump inhibitor) such as Prevacid or Nexium; and
3. A Cox-2 inhibitor (cyclooxygenase 2-selective inhibitor) alone, such as Vioxx or Celebrex.

The study marks the first time researchers have looked at the cost-effectiveness of a popular combination of two drugs and also included other factors that may affect therapy, such as aspirin use and the risk of complications such as heart attack.

According to researchers, the study also looked at the health economic consequences of heart attacks related to Cox-2 inhibitors like Vioxx. The study, completed a year before Vioxx was removed from the market in September 2004, not only predicted the cardiovascular complications, but also demonstrated that a combination therapy of two other drugs may prove more cost-effective and safer than Cox-2s.

"We found that for high-risk patients, the combination of a common anti-inflammatory drug taken with an acid-lowering drug was not only less expensive, but also safer and more effective. Cox-2 inhibitors were not a health economic bargain at all - especially given the added costs of more heart attacks," says Dr. Brennan M.R. Spiegel, study author and co-director, Center for the Study of Digestive Healthcare Quality and Outcomes and assistant professor of medicine, David Geffen School of Medicine at UCLA and VA Greater Los Angeles Healthcare System.

More than 15 million Americans suffer from chronic arthritis, including osteoarthritis and rheumatoid arthritis. According to researchers, non-steroidal anti-inflammatory drugs (NSAID) are the most commonly used medications for chronic arthritis, but can cause gastrointestinal complications such as ulcers and hemorrhages in high-risk patients.

The UCLA study found that for high-risk patients, it is more cost-effective and safer to use a non-steroidal anti-inflammatory drug combined with a proton pump inhibitor, which is an acid-lowering drug, compared to using a Cox-2 inhibitor drug alone, which guidelines had traditionally recommended as a first-line therapy for this patient group. According to the study, for patients at low risk of gastrointestinal problems, a non-steroidal anti-inflammatory drug alone proved the most cost-effective.

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Pain relief options after Vioxx and Bextra recalls

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Celebrex recall demanded

Pain relief options after Bextra and Vioxx recalls

After news of Vioxx recall, Bextra recall, and addition of a black box warning on Celebrex came out, arthritis patients are seeking other alternatives for pain relief. While these drugs were heavily advertised as some kind of miracle drugs for pain relief, research published during last six months has clearly shown that they were hyped to people who needed them the least. In this article, we discuss two choices for patients.

Apart from many other drugs for pain relief, Animi-3, a prescription medication from PBM Pharmaceuticals, contains ingredients that may have a beneficial, protective effect in inflammatory diseases such as rheumatoid arthritis (RA). The only Rx product of its kind, Animi-3 contains the omega-3 fatty acids DHA and EPA, and a combination of three important B vitamins -- prescription strength folic acid, plus vitamins B6 and B12. The omega-3 fatty acids in Animi-3 are exclusive, DHA dominant, and highly refined.

Patients may also wish to consider the benefits of physical therapist intervention for pain relief from certain conditions, according to the American Physical Therapy Association (APTA). "Many people are looking for alternatives to the sole use of medication to deal with painful conditions," said APTA President Ben F Massey, Jr, PT, MA. "Pain medication may help you get through periods of severe pain, but it won't always help you eliminate the underlying cause of some kinds of pain. For many individuals, it is the underlying causes like poor posture and alignment, weak and/or inflexible muscles, or tight joint structures that actually exacerbate the painful condition," Massey explained. "A physical therapist will perform a complete musculoskeletal examination and design an individualized treatment program to reduce pain and improve function."

There are many types of pain and inflammation that can be reduced by physical therapist intervention. For example, chronic pain in the back, shoulder, or knee, or pain associated with certain degenerative diseases such as osteoarthritis, can be reduced with the appropriate combination of medication and exercise. "The physical therapist, in collaboration with the patient and the patient's physician, can help the patient manage his or her health over the long term," explained Massey.

For pain of a "mechanical" origin such as back, shoulder, or knee pain, physical therapist intervention may include therapeutic exercise, manual therapy, and functional training. "The goal of the physical therapist is to reduce pain, improve your ability to perform daily activities, and help the individual return to doing the things he or she likes to do," said Massey. "It is also true that patients may unknowingly contribute to their own pain, such as by exercising improperly or with poor posture that physical therapists can identify and help to correct."

For osteoarthritis, a degenerative disease of the cartilage and bone, physical therapist intervention may include exercises for strength, flexibility, range of motion, and devices designed to rest or support the joint such as orthotics or splints.

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Topical cream for Vioxx, Celebrex, and Bextra users

Safe use of over-the-counter pain relief drugs after recall of Vioxx and Bextra

Sources: APTA and PBM Pharmaceuticals

Bextra recall leaves Pfizer credit rating intact for the time being

After Vioxx recall, it has simply been downhill for Merck. Not only has it been a target of numerous Vioxx recall related class action lawsuits, its credit rating has suffered. Apparently that is not the case for Pfizer. After Bextra recall and addition of a black-box warning on Celebrex, Fitch Ratings notes that the 'AAA' rating and stable outlook of Pfizer will not be affected.

Celebrex accounted for $3.3 billion in revenue (6.3% of total Pfizer sales), and Bextra accounted for $1.2 billion in revenue (2.4% of sales) in 2004. Pfizer generated $52.5 billion in total revenues in 2004. The withdrawal of Bextra will have an immediate impact on Pfizer sales; however, the degree to which Celebrex sales are affected is difficult to ascertain, considering the FDA is requiring similar warnings on drugs (including over-the-counter pain medications) that compete with Celebrex. Fitch anticipates that Celebrex (whose patent expires in 2013) sales will be negatively affected but the product will continue to generate between $1.5 billion to $2.5 billion in sales in 2005 and that sales growth is likely to rebound in 2006.

Finally, Fitch notes Pfizer's 'AAA' rating is further supported by the company's still superior liquidity, cash flow, and modest debt burden. Despite the loss of cash flow related to the Cox-2 drugs and pending patent expirations, Fitch anticipates that Pfizer will still continue to generate free cash flow (net cash flow from operating activities less capital expenditures and dividends) in excess of $5 billion. Furthermore, Pfizer has nearly $20 billion of cash on its balance sheet and has announced its board has approved a $29 billion repatriation plan under the Homeland Investors Act.

Additionally, a recently announced $4 billion restructuring plan should serve to support margins during the next several years while the company faces patent expirations, flat growth expectations for 2005, and industry-related challenges such as the pending Medicare drug bill.

While Pfizer is also a target of lawsuits related to Celebrex and Bextra, the number was much smaller than those for Vioxx personal injury lawsuits. With the announcement regarding recall of Bextra, though, it is expected that Pfizer's Bextra liabilities may skyrocket, exposing the company to same risks as Merck. That could lower its credit rating later.

Recommended article: Celebrex and Bextra problems do hurt Pfizer financially

Source: Fitch Ratings

Celebrex recall demanded despite Bextra withdrawal

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. Yesterday, the U.S. Food and Drug Administration (FDA) 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 agency's 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 FDA's operations, to investigate why the agency is not also pulling the equally dangerous Celebrex from the shelves.
- By Sidney M. Wolfe, M.D., Director, Public Citizen's Health Research Group

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Vioxx side effects confirmed in another study

In a report titled "The Risk for Myocardial Infarction with Cyclooxygenase-2 Inhibitors: A Population Study of Elderly Adults," published in the Annals of Internal Medicine, the authors L.E. Lévesque, J.M. Brophy, and B. Zhang, find that people prescribed rofecoxib (Vioxx) had a 1.24 higher relative risk for heart attack compared to those prescribed no NSAIDs. Higher doses of rofecoxib were associated with higher risks. Concomitant aspirin use lessened the risks associated with low-dose, but not high-dose, rofecoxib. (Related article: Vioxx doubled risk of heart attacks)

Celecoxib (Celebrex), meloxicam (Mobicox), and the other NSAIDs were not associated with increased risk for heart attack. The researchers studied 113,927 adults older than 65 years of age in Québec, Canada. (Related article: Merck argues that both Vioxx and Celebrex have same risks)

Apart from confirming that Vioxx did lead to higher rate of heart attack, something that Merck continues to deny, this study has other implications as well. Some nonselective NSAIDs and COX-2 inhibitors (e.g. Celebrex, Bextra, Arcoxia, etc.), other than Vioxx, might not increase the risk for a heart attack, the study found. In other words, it is a strong endorsement of the position of Vioxx victims who are involved in litigation with Merck but victims of Celebrex and Bextra will need to rely on several other studies to support their argument. (Related article: Celebrex class action lawsuits)

Doctors agree that Vioxx, Celebrex, and Bextra do have a few benefits but they also bring many other risks with them. In an excellent article, Robert A. Greenwald, M.D., Professor of Medicine at Albert Einstein College of Medicine, says, "Aggressive marketing by the manufacturers of the COX-2 drugs backfired into the current controversy. The drugs were originally intended only for high-risk populations, e.g., the elderly, those with prior gastrointestinal events, etc. A forty-year old male with a tennis elbow and no ulcer history was not the target population for these drugs. Over-enthusiasm for prescribing the COX-2 drugs has now backlashed into over-avoidance. Had the COX-2 agents been restricted to the populations for which they were originally intended, they might still be enjoying widespread use, and their potential for other, lifesaving indications would still be under exploration, and not on the shelf. Let us hope the recent FDA decision to keep the drugs on the market enables their most beneficial uses to continue, including any yet to be discovered." (Related article: Will you take Vioxx if it returns?)

In the meantime, Merck continues to struggle as a company. The management has essentially dealt with the problem by violating what it touts as its guiding principles, that is, "dedicated to putting patients first" and "Committed to bringing out the best in medicine." It has refused to accept any responsibility whatsoever for the estimated 140,000 deaths and injuries from Vioxx. It has laid off thousands of employees after Vioxx recall and continues to be in denial about the challenges that it faces. In a study by Vault (a company that tries to find out the "insider" information for prospective employees), finds that, "Employee morale at Merck is said to be at an all time low following the layoff of 5,200 employees and the withdrawal of Vioxx, one of the company's largest drugs. Blockbusters are coming off patent and there are no visible replacements in the pipeline. Employee turnover has more than doubled."

No wonder then that the FDA has not given a green signal yet to Merck to sell Vioxx again and has simply indicated that it will evaluate Merck's request to do so. It seems highly unlikely that Vioxx will be back on the market considering that Bextra recall has been announced by the FDA and Celebrex will carry a black-box warning.

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Useful links
Annals of Internal Medicine
Albert Einstein College of Medicine
Vault

Celebrex to carry black box warning

Apart from announcing that Pfizer will recall Bextra, the US Food & Drug Administration (FDA) also announced that it has asked Pfizer to include a boxed warning in the Celebrex (celecoxib) label. Pfizer has agreed to suspend sales and marketing of Bextra in the U.S., pending further discussions with the agency. Pfizer has also agreed to work with FDA on the boxed warning for Celebrex. (Related article: Bextra recall announced)

This decision was expected since a series of studies had shown that Celebrex had serious side effects. After Vioxx recall was announced by Merck in September 2004, several doctors and consumer groups had demanded a recall of Celebrex as well. A FDA panel agreed in February 2005 that Celebrex had severe side effects but it had some benefits, and therefore, should be allowed to stay on the market with a black-box warning (the most serious warning on an approved drug in the United States).

Since early reports of Celebrex side effects started to pour in late last year, Americans have continued to abandon Celebrex. While the company saw a huge increase in sales after the recall of Vioxx, there was an equally steep drop in sales after the data on side effects were published. During this saga, Pfizer, however, continued to stand by the safety of Celebrex. The FDA also warned Pfizer for misleading ads related to Celebrex.

In an announcement, Pfizer said today it will work with the FDA to add expanded risk information in the Celebrex label following an FDA decision to require boxed warnings of potential cardiovascular risk for all COX-2 pain relievers and all NSAIDs, including older non-specific drugs such as ibuprofen and naproxen (Aleve).

Pfizer and the FDA plan further discussions regarding the precise content of the Celebrex label. Pfizer says that it has accumulated extensive Celebrex clinical data over the past 10 years involving more than 40,000 patients. Pfizer also reaffirmed its commitment to conduct additional long-term clinical studies evaluating the benefits and risks of Celebrex. Pfizer also said it will work closely with the FDA to develop a guide to assist patients and their healthcare professionals in making the best decisions for treating their arthritis pain.

FDA is allowing Celebrex to remain on the market on the condition that Pfizer take the actions listed below.

• Revise the Celebrex label to include a boxed warning containing the class NSAID warnings and contraindication about cardiovascular and gastrointestinal risk, plus specific information on the controlled clinical trial data that demonstrate an increased risk of adverse CV events for celecoxib, and encourage prescribers to discuss with patients the potential benefits and risks of Celebrex and other treatment options before a decision is made to use Celebrex.
• Encourage practitioners to use the lowest effective dose for the shortest duration consistent with individual patient treatment goals.
• Include a Medication Guide as part of the labeling. It will be required to be given at the time the drug is dispensed to inform patients of the potential for CV and GI risk associated with NSAIDS, in general, and Celebrex specifically. The Medication Guide will inform patients of the need to discuss with their doctor the risks and benefits of using NSAIDs and the importance of using the lowest effective dose for the shortest duration possible.
• Commit to conduct a long-term study to address the safety of Celebrex compared to naproxen and other appropriate drugs. FDA will work with Pfizer to design this long-term study and ensure its timely initiation and completion.

Finally, the FDA is advising patients, who are taking CELEBREX, that they should discuss questions or concerns about this new information with their physician.

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Adderall patch results come out positive

Shire Pharmaceuticals Group today announced positive preliminary results from clinical trials of its methylphenidate transdermal system (MTS) which is being developed in conjunction with Noven Pharmaceuticals for children with attention deficit and hyperactivity disorder (ADHD). "Shire aims to have a range of medicines in its ADHD portfolio, with ADDERALL XR being the most prescribed treatment for ADHD in the US. If approved, this product will be a strong addition and we look forward to advancing its development further,” Matthew Emmens, Chief Executive Officer of Shire, said in a statement.

It may be recalled that due to serious safety concerns Health Canada forced Shire to recall Adderall. The FDA, on the contrary, has refused to take any action. If the FDA approves this new product, it will be a big setback to those consumers who have been demanding that FDA also act in this matter. (Related article: Adderall recall)

Shire will release additional details of the trial results following further analysis and as part of an R&D update in May 2005. Emmens added, “These results demonstrate that MTS has the potential to provide significant benefits for children with ADHD, especially those that have difficulty taking oral medications and those that find a once-a-day patch more appropriate for their lifestyle. As the ADHD market develops, new choices of treatment are emerging, including specialized delivery systems (such as MTS) to meet the needs of different patients."

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Nexium as an alternative after Vioxx recall

After Vioxx recall in September of 2004, the first beneficiaries were Celebrex and Bextra, two drugs that were aggressively marketed the very same day by Pfizer. The party did not last all that long since in early December, news started to pour in about their side effects. A series of studies were presented during this period and in February, a panel of experts concluded that Vioxx, Celebrex, and Bextra were essentially all bad drugs but since the panel had many members with ties to both Pfizer and Merck, it recommended that the drugs be brought back on the market. A decision from the FDA is expected soon but for all those Americans who never read a newspaper or watch the news on TV, this is a very dangerous situation. (Related article: Will you take Vioxx if it returns?)

Since then Mobic has become a popular alternative and so have Aleve, ibuprofen, etc. Interestingly enough, even some natural alternatives to Vioxx have been offered. But an unexpected drug is also benefiting from the controversy over Cox-2 drugs. Patients are switching to older anti-inflammatories (e.g. aspirin) in combination with ulcer drugs known as proton-pump inhibitors. Those drugs include Nexium, Prilosec, Prevacid and Protonix.

In the US alone, Nexium sales are up 10% while in other markets they are up 29%. This will all be great if Nexium were a wonderful deal for American consumers. Well it so turns out that Nexium is nothing but Prilosec (whose patent has expired, and since it is now made by many more drugmakers now, the prices are dirt cheap), but sold at a significantly higher price, all because of slick direct-to-consumer advertising by AstraZeneca. Lawsuits are pending  against the firm for misleading consumers.

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