Evelyn Pringle April 12, 2007
The anti-epileptic drug, Depakote (valproate), marketed by Abbott Laboratories, is one of the most heavily prescribed medications for off-label use. Experts say the evidence of harm caused by Depakote is just beginning to emerge.
According to Harrisburg, Pennsylvania psychiatrist, Dr Stefan Kruszewski, a recognized expert on psychotropic drugs, "we can anticipate a continuing series of tragic outcomes from the massive overuse of Depakote, secondary not only to birth defects and death, but also due to anemias, hepatic disease, obesity, diabetes type II, pancreatitis and other serious systemic and neurological dysfunctions."
Bayer is under fire for hiding the adverse effects of the anti-clotting drug, Trasylol, used in heart surgery, and will no doubt be hit with plenty of lawsuits in the not to distant future, considering that Dr Dennis Mangano, the lead author of new study in the February 7, 2007, Journal of the American Medical Association, says that the Trasylol may be responsible for 10,000 deaths over five years.
On December 15, 2006, the FDA announced new labeling for Trasylol, and said a study suggests that, in addition to serious kidney damage, Trasylol may increase the chance for death, congestive heart failure (a weakening of the heart), and strokes.
Because Trasylol is administered during surgery, many victims may not even realize they have been injured by the drug. But plenty have, according to Dr Mangano, who says that in 2006, Trasylol, was administered to 246,000 patients.
Another drug on the legal chopping block is the Parkinson's drug, Permax. As far back as December 2002, doctors at the Mayo Clinic reported heart valve disease in 3 patients who had been taking Permax, similar to damage caused by the Fen-Phen combination.
In 2004, HealthDay News reported that a study had confirmed previous findings that the drug could damage heart valves and surgery would be needed to correct it. Two new studies in the January 4, 2007, New England Journal of Medicine, report that the number of Permax patients who have developed valve damage is higher than expected.
One study, which included 155 patients taking various Parkinson's drugs, and 90 healthy patients in a comparison group, and found moderate to severe valve problems in more than 23% of the patients on Permax, compared to less than 6% in the comparison group.
The second study found Permax users were 5 to 7 times more likely to have leaky heart valves than patients taking other types of Parkinson's drugs, and patients taking the highest doses of Permax had a 37 times greater risk.
"This is not a rare side effect," says Dr Bryan Roth, a professor at the University of North Carolina, who wrote an editorial accompanying the reports in the NEJM.
"That's an extraordinarily high incidence," he warns. "That makes this a serious problem."
Heart valve damage is a life-threatening condition and costly to treat. Replacement requires open heart surgery, where the breastbone is divided, the heart is stopped, and blood is sent through a heart-lung machine, according to the Texas Heart Institute. No drug can reverse valve damage, making replacement surgery the only option. Medical experts are advising all Permax patients to undergo testing for valve damage.
The drug was introduced to the US market by Eli Lilly, but Valeant Pharmaceuticals now sells Permax. On March 29, 2007, Permax was pulled off the market after the FDA reviewed new information that associates it with heart problems.
During the last 2 decades, the antidepressants, known as selective serotonin reuptake inhibitors, or SSRIs, have been prescribed for more unapproved uses than any other class of drugs in history. A June 2005, study in the Journal of Clinical Psychiatry, found that 75% of SSRI prescriptions written were for unapproved uses.
SSRIs have now been linked to suicidality, extreme violence and homicide, several life-threatening birth defects, abnormal uterine or gastrointestinal bleeding, a decrease in bone mineral density, fertility problems, sexual dysfunction, and a severe withdrawal syndrome.
On April 10, 2004, the British Medical Journal, criticized the authors of studies on SSRI's for exaggerating the benefits and downplaying the harm, including suicidality, and discussed a study of 93 children on Paxil that produced 11 serious adverse events, including 7 hospitalizations, compared to only 2 in children in the placebo group.
The Paxil suicide risk is not limited to children. An August 22, 2005, study by Norwegian researchers of over 1,500 adults, found 7 Paxil patients attempted suicide compared to only 1 attempt in the group on a placebo, and recommended that warnings not to prescribe Paxil to children should also apply to adults.
According to Forest Lab's Annual Report filed on June 14, 2006, the company is a named defendant in approximately 25 lawsuits, with the majority involving the company's top selling SSRI drugs, Celexa or Lexapro, for inducing suicidality.
A wrongful death lawsuit was filed in September 2005, by the Pogust & Braslow law firm in Conshohocken, Pennsylvania, on behalf of the family of 32-year-old man who unexpectedly committed suicide soon after being prescribed Lexapro.
A steady stream of lawsuits have been filed against GlaxoSmithKline over Paxil, stemming from the company's concealment of the drug's link to suicide, birth defects, violence and withdrawal syndrome.
On March 23, 2006, the California-based Baum Hedlund law firm filed a national class-action lawsuit against Glaxo on behalf of the mother of an 11-year old Kansas boy who committed suicide, and a teenager in Texas who attempted suicide while taking Paxil.
She says, Baum Hedlund has documents obtained in litigation that show there was an awareness of the suicide risk as far back as the late 1970's, a decade before the first SSRI was approved for sale in the US.
A new round of Paxil lawsuits began on October 16, 2006, when Baum Hedlund filed a case alleging that Paxil use during pregnancy resulted in an infant being born with a life-threatening lung disorder, PPHN. Between 10% and 20% of infants born with PPHN end up dying, even when they receive treatment.
On July 28, 2006, Baum Hedlund also filed a lawsuit on behalf of the parents of an infant who was born with congenital heart birth defects as a result of his mother taking Paxil during pregnancy. Since birth, the child has undergone 3 open-heart surgeries and will likely have to undergo more and possibly a heart transplant at some point in the future.
Based on the company's legendary history of concealing adverse effects, the lead attorney on the case, Karen Barth Menzies, says believes Glaxo has known about these risks and should have warned prescribing doctors and consumers about these birth defects long ago.
The Houston law firm of Robert Kwok & Associates is handling a Celexa birth heart defects case in Kentucky. The mother was prescribed Celexa during pregnancy, and her baby was born with Shone's Complex, a form of congenital heart disease that consists of defects that lead to the obstruction of blood flow from the heart to the body.
Legal analysts are predicting that SSRI makers will offer early settlements in cases involving birth defects to avoid having these families appear before a jury.
Pfizer is still being sued left and right over adverse effects related to the epilepsy drug Neurontin. In 2004, the company pleaded guilty to charges involving a massive off-label marketing scheme and agreed to pay the second-largest settlement ever in a health care fraud prosecution of $403 million. By 2002, a full 94% of Neurontin sales were for off-label use, according to the August 16, 2004 USA Today.
Many private lawsuits involve Neurontin-induced suicidality. The Pogust & Braslow law firm is handling a case for Natalie Biedenbender, whose husband committed suicide at age 39, after being prescribed the drug off-label for back pain.
"Although Neurontin is prescribed for scores of off-label indications," Attorney Derek Braslow reports, "since 1999, the off-label use continues to be most common in the areas where the company focused its illegal marketing efforts, such as bipolar disorder, peripheral neuropathy, and migraine."
Two lawsuits were recently filed against Novartis and Astellas Pharma, the makers of the topical skin creams, Elidel and Protopic, used to treat eczema. Alan and Dayna Thomson filed a lawsuit in December 2006 after their daughter Haley died after using Elidel, and Ashley McDonald filed a lawsuit in January 2007 after being diagnosed with lymphoma following her use of Elidel.
In another case, Traci Reilly, of Naperville, Illinois, developed breast cancer after applying Protopic and Elidel for a condition that caused patches of discolored skin on her breast.
Protopic and Elidel belong to a class of drugs known as calcineurin inhibitors, so called because they reduce immune activity by inhibiting the activity of the enzyme calcineurin in organ transplant patients. Use of these drugs has long been known to increase the risk of cancer, and the drugs were labeled accordingly for use in transplant patients.
Protopic and Elidel have only been on the market for about 5 years and together have already been prescribed to more than 7 million people. In 2006, the FDA added a black box warning to the skin creams about the cancer risk.
On February 21, 2007, Tom Moore, the author of several books on the pharmaceutical industry, told CBS News that he had studied about 1,200 cases of suspected injuries pertaining to Protopic and Elidel reported to the FDA through 2005 and found more than 100 potential cancer cases in children and adults, with most involving lymphoma or skin cancer.
Showing posts with label Permax. Show all posts
Showing posts with label Permax. Show all posts
Saturday, August 7, 2010
Experts Predict Many Cases of Permax Heart Valve Damage
Evelyn Pringle January 21, 2007
Nearly three years ago, HealthDay News reported that a study had confirmed previous findings that the drug, Permax, used to treat Parkinson's disease, could damage heart valves and surgery would be needed to correct the problem.
The April 28, 2004, report quoted the lead researcher, Dr Richard Dewey Jr, an associate professor from the University of Texas Southwestern Medical Center, as saying he believed the drug should be taken off the market.
Permax (pergolide) belongs to a class of drugs known as dopamine agonists. Dopamine helps regulate movement and balance. People with Parkinson's suffer from a shortage of dopamine and Permax stimulates nerves in the brain that would normally be stimulated by dopamine. The drug has also been prescribed to treat restless leg syndrome.
Two years earlier, in December 2002, doctors at the Mayo Clinic reported heart valve disease in three patients who had been taking Permax for several years, similar to the damage found in patients who took the Fen-Phen diet drugs.
The 3 cases involved women aged 61, 72, and 74, with no history of heart disease, who had been taking Permax for between three and seven years to treat Parkinson's symptoms. They were all diagnosed with serious valve disease and two required replacement surgery.
As a follow-up to the earlier reports of valve damage in Permax patients, Dr Dewey, and his fellow researchers sent out 200 letters to people who were known to be taking Permax for Parkinson's to determine whether the reports were isolated cases or a common side effect of the drug, and to suggest that patients should switch to anther drug. Patients who wanted to continue taking Permax were urged to have an echocardiogram, to check for heart valve damage.
For the Dewey study, echocardiograms were performed on 46 patients, and then compared the test results from a similarly-aged healthy comparison group. The study found that 89% of the patients receiving Permax had evidence of leaky heart valves, called valvular insufficiency, and Permax patients were up to 18 times more likely to have significant leakage in at least one valve, than patients in the comparison group.
Blood is pumped through the heart in only one direction, according to the Texas Heart Institute. Heart valves play a key role in this one-way blood flow, opening and closing with each heartbeat. Pressure changes on either side of the valves cause them to open their flap-like "doors" at just the right time, then close tightly to prevent a backflow of blood. There are 4 valves in the heart:
* Tricuspid valve
* Pulmonary valve
* Mitral valve
* Aortic valve
Valvular insufficiency occurs when the heart valves do not close properly. It forces the heart to work harder to circulate the blood and can lead to serious problems such as heart attack or heart failure, according to WebMD. Symptoms of heart valve disease include:
* Shortness of breath and/or difficulty breathing
* Weakness or dizziness
* Chest pain or pressure
* Heart palpitations
* Swelling of ankles, feet, or abdomen
* Rapid weight gain
Two new studies published in the January 4, 2007, New England Journal of Medicine, report that the number of Parkinson patients on Permax who have developed heart valve damage is higher than expected.
In one study titled, "Dopamine Agonists and the Risk of Cardiac-Valve Regurgitation," researchers led by Dr Renzo Zanettini, in Milan, Italy obtained echocardiograms from 155 patients taking various Parkinson's drugs, and 90 healthy patients for a comparison group.
The study found moderate to severe valve problems in more than 23% of the patients receiving Permax compared to less than 6% of the patients in the comparison group.
The second study found that Permax users were five to seven times more likely to have leaky heart valves than patients taking other types of Parkinson's drugs, and patients taking the highest doses of Permax had a 37 times greater risk of valve damage. In this study, Dr Rene Schade and colleagues in Berlin and Montreal reviewed records from over 11,400 patients with Parkinson's disease in the UK.
"This is not a rare side effect," says Dr Bryan Roth, a pharmacology professor at the University of North Carolina, who wrote an editorial accompanying the reports in the NEJM. "That's an extraordinarily high incidence," he warns. "That makes this a serious problem."
Experts note that there are no medications that can be used to reverse valve damage and replacement surgery is the only solution.
Dr Roth published a paper several years ago warning that Permax appeared to trigger the same heart valve problems as the Fen-Phen combination of the drugs, Pondimin and Redux, which were pulled off the market in 1997, after they were linked to valve disease.
The findings of the new Permax studies could potentially represent a public health crisis. The drugs, available in generic form from a variety of producers, "have been around a long time, and a large number of people have potentially been exposed to them," said Dr Michael Okun, medical director of the National Parkinson Foundation, in the January 4, 2007 LA Times.
Permax came on the market in the US about 14 years ago, and an estimated half million people had already taken the drug by the time its maker, Eli Lilly, added valve damage to the side effects listed on the labeling in late 2003. The warning included the statement: "Some patients have required valve replacement, and deaths have been reported," but at the same time, Lilly claimed that the problem only occurred in five out of every 100,000 Permax users.
The drug is now marketed in the US by Valeant Pharmaceuticals.
Heart valve damage is an extremely serious medical condition that is both life-threatening and costly to treat. During valve replacement surgery, the breastbone is divided, the heart is stopped, and blood is sent through a heart-lung machine. Because the heart or aorta must be opened, it requires open heart surgery, according to the Texas Heart Institute.
The two kinds of valves used for replacement surgery are mechanical valves made from materials such as plastic or metal, and biological valves made from animal tissue or human tissue from a donated heart.
Mechanical valves are stronger and last longer but because blood tends to stick to them and create blood clots, patients need to take blood-thinning drugs for the rest of their lives. And because these medicines increase the risk of bleeding within the body, patients must always wear a medical alert bracelet so medical professionals will know they are taking a blood-thinning medication.
Patients with biological valves usually do not have to take blood-thinning drugs but because the valves are not as strong as mechanical valves patients may need have the valve replaced every 10 years.
Following surgery, a patient can expect to stay in the hospital for about a week, including at least 1 to 3 days in the Intensive Care Unit, the Texas Institute says. Patients with an office job, can usually go back to work in 4 to 6 weeks but those with more physically demanding jobs may need to be off work longer.
In addition to switching to another drug to treat Parkinson's disease, medical experts are advising all Permax patients to undergo testing to check for heart valve damage.
Nearly three years ago, HealthDay News reported that a study had confirmed previous findings that the drug, Permax, used to treat Parkinson's disease, could damage heart valves and surgery would be needed to correct the problem.
The April 28, 2004, report quoted the lead researcher, Dr Richard Dewey Jr, an associate professor from the University of Texas Southwestern Medical Center, as saying he believed the drug should be taken off the market.
Permax (pergolide) belongs to a class of drugs known as dopamine agonists. Dopamine helps regulate movement and balance. People with Parkinson's suffer from a shortage of dopamine and Permax stimulates nerves in the brain that would normally be stimulated by dopamine. The drug has also been prescribed to treat restless leg syndrome.
Two years earlier, in December 2002, doctors at the Mayo Clinic reported heart valve disease in three patients who had been taking Permax for several years, similar to the damage found in patients who took the Fen-Phen diet drugs.
The 3 cases involved women aged 61, 72, and 74, with no history of heart disease, who had been taking Permax for between three and seven years to treat Parkinson's symptoms. They were all diagnosed with serious valve disease and two required replacement surgery.
As a follow-up to the earlier reports of valve damage in Permax patients, Dr Dewey, and his fellow researchers sent out 200 letters to people who were known to be taking Permax for Parkinson's to determine whether the reports were isolated cases or a common side effect of the drug, and to suggest that patients should switch to anther drug. Patients who wanted to continue taking Permax were urged to have an echocardiogram, to check for heart valve damage.
For the Dewey study, echocardiograms were performed on 46 patients, and then compared the test results from a similarly-aged healthy comparison group. The study found that 89% of the patients receiving Permax had evidence of leaky heart valves, called valvular insufficiency, and Permax patients were up to 18 times more likely to have significant leakage in at least one valve, than patients in the comparison group.
Blood is pumped through the heart in only one direction, according to the Texas Heart Institute. Heart valves play a key role in this one-way blood flow, opening and closing with each heartbeat. Pressure changes on either side of the valves cause them to open their flap-like "doors" at just the right time, then close tightly to prevent a backflow of blood. There are 4 valves in the heart:
* Tricuspid valve
* Pulmonary valve
* Mitral valve
* Aortic valve
Valvular insufficiency occurs when the heart valves do not close properly. It forces the heart to work harder to circulate the blood and can lead to serious problems such as heart attack or heart failure, according to WebMD. Symptoms of heart valve disease include:
* Shortness of breath and/or difficulty breathing
* Weakness or dizziness
* Chest pain or pressure
* Heart palpitations
* Swelling of ankles, feet, or abdomen
* Rapid weight gain
Two new studies published in the January 4, 2007, New England Journal of Medicine, report that the number of Parkinson patients on Permax who have developed heart valve damage is higher than expected.
In one study titled, "Dopamine Agonists and the Risk of Cardiac-Valve Regurgitation," researchers led by Dr Renzo Zanettini, in Milan, Italy obtained echocardiograms from 155 patients taking various Parkinson's drugs, and 90 healthy patients for a comparison group.
The study found moderate to severe valve problems in more than 23% of the patients receiving Permax compared to less than 6% of the patients in the comparison group.
The second study found that Permax users were five to seven times more likely to have leaky heart valves than patients taking other types of Parkinson's drugs, and patients taking the highest doses of Permax had a 37 times greater risk of valve damage. In this study, Dr Rene Schade and colleagues in Berlin and Montreal reviewed records from over 11,400 patients with Parkinson's disease in the UK.
"This is not a rare side effect," says Dr Bryan Roth, a pharmacology professor at the University of North Carolina, who wrote an editorial accompanying the reports in the NEJM. "That's an extraordinarily high incidence," he warns. "That makes this a serious problem."
Experts note that there are no medications that can be used to reverse valve damage and replacement surgery is the only solution.
Dr Roth published a paper several years ago warning that Permax appeared to trigger the same heart valve problems as the Fen-Phen combination of the drugs, Pondimin and Redux, which were pulled off the market in 1997, after they were linked to valve disease.
The findings of the new Permax studies could potentially represent a public health crisis. The drugs, available in generic form from a variety of producers, "have been around a long time, and a large number of people have potentially been exposed to them," said Dr Michael Okun, medical director of the National Parkinson Foundation, in the January 4, 2007 LA Times.
Permax came on the market in the US about 14 years ago, and an estimated half million people had already taken the drug by the time its maker, Eli Lilly, added valve damage to the side effects listed on the labeling in late 2003. The warning included the statement: "Some patients have required valve replacement, and deaths have been reported," but at the same time, Lilly claimed that the problem only occurred in five out of every 100,000 Permax users.
The drug is now marketed in the US by Valeant Pharmaceuticals.
Heart valve damage is an extremely serious medical condition that is both life-threatening and costly to treat. During valve replacement surgery, the breastbone is divided, the heart is stopped, and blood is sent through a heart-lung machine. Because the heart or aorta must be opened, it requires open heart surgery, according to the Texas Heart Institute.
The two kinds of valves used for replacement surgery are mechanical valves made from materials such as plastic or metal, and biological valves made from animal tissue or human tissue from a donated heart.
Mechanical valves are stronger and last longer but because blood tends to stick to them and create blood clots, patients need to take blood-thinning drugs for the rest of their lives. And because these medicines increase the risk of bleeding within the body, patients must always wear a medical alert bracelet so medical professionals will know they are taking a blood-thinning medication.
Patients with biological valves usually do not have to take blood-thinning drugs but because the valves are not as strong as mechanical valves patients may need have the valve replaced every 10 years.
Following surgery, a patient can expect to stay in the hospital for about a week, including at least 1 to 3 days in the Intensive Care Unit, the Texas Institute says. Patients with an office job, can usually go back to work in 4 to 6 weeks but those with more physically demanding jobs may need to be off work longer.
In addition to switching to another drug to treat Parkinson's disease, medical experts are advising all Permax patients to undergo testing to check for heart valve damage.
Sunday, August 1, 2010
FDA Finally Yanks Permax Off the US Market
Evelyn Pringle April 4, 2007
On March 29, 2006, the FDA withdrew Permax (pergolide) from the market because it increases the risk of valvular heart disease. Permax belongs to a class of drugs known as dopamine agonists that help regulate balance and movement in Parkinson's patients who suffer from a lack of dopamine.
When Permax was FDA approved in 1988, Eli Lilly marketed the drug, but in the US today, the drug is manufactured by Valeant Pharmaceuticals and generic versions are sold by Par and Teva. According to IMS Health, a prescription drug tracking firm, more than 72,000 prescriptions for the drug were written in 2006.
The decision by the FDA to take Permax off the market came after 2 recent studies were published in the New England Journal of Medicine in January 2007, that confirmed previous studies that linked Permax, and another drug prescribed to treat Parkinson's disease, Dostinex, to heart valve disease.
Dostinex is marketed by Pfizer, and is approved to treat Parkinson's patients in other countries. However, the drug has only been approved to treat the hormonal disorder, hyperprolactinemiam in the US, which means any prescriptions for Dostinex written for Parkinson's patients in this country were off-label, because the drug has never passed the required FDA approval process to demonstrate that it is safe and effective in treating patient's with Parkinson's disease.
The NEJM studies did not assess patients who were taking Dostinex for the hormonal disorder, and according to Dr Shlomo Melmed, an endocrinologist and a senior vice president of Cedars-Sinai Medical Center in Los Angeles, in the January 4, 2007, New York Times, tens of thousands of people in the US, mostly women, have taken the drug for hyperprolactinemiam.
Experts say the valve damage is not likely to be profound in patients treated for the hormone disorder because lower doses of Dostinex are used compared to Parkinson's patients, but Dr Melmed told the Times that men can develop the condition and may need higher doses, so those men should be monitored for heart valve damage.
In 2003, Eli Lilly first added the risk of heart valve damage to the Permax label but by then an estimated half million people had already taken the drug. Although the warning stated: "Some patients have required valve replacement, and deaths have been reported," Lilly said at the time that only 5 out of 100,000 patients developed valve damage.
The company also sent out a Dear Dr letter to prescribing doctors to warn about the increased risk in 2003, but the FDA did not add a black box warning about valve damage to the label on Permax until 2006. A "precaution" was also added to the label of Dostinex in December 2006.
Heart valve damage is a life-threatening condition that can lead to heart failure and sudden death. It cannot be treated with medication and open heart surgery for valve replacement is the only option available for patients with valve disease.
The surgery itself is complex, costly, and life-threatening. According to the Texas Heart Institute, for valve replacement surgery, the breastbone must be divided, the heart stopped, and blood must filtered through a heart-lung machine.
Following surgery, the Institute says, patients must be maintained in the Intensive Care Unit for one to 3 days, and patients typically remain hospitalized for about a week.
There are 2 types of valves used for replacement. Mechanical valves, which are made with plastic or metal, and biological valves which are made with animal tissue or human tissue from a donated heart.
Experts say, mechanical valves last longer than biological valves but blood tends to stick to devices, causing blood clots to form and patients often need to take a blood-thinning drug for life. Because blood thinners are known to increase the risk of bleeding within the body, patients taking the drugs must wear a medical alert bracelet at all times so medical professionals will know they are on the medication.
Patients with biological valves are usually not required to take blood-thinners but these valves are not as sturdy as the mechanical valves and often need to be replaced every 10 years.
According to FDA officials, to date the agency is aware of at least 14 cases where patients have required replacement surgery, but Dr Robert Temple of the FDA's office of drug evaluation, said at a briefing that 14 is likely to be an underestimate.
The FDA has consistently acknowledged on may occasions that only between 1% and 10% of all adverse events associated with prescription drugs are reported through the agency's data tracking system which means the actual number of patients with valve damage is bound to be much higher.
The FDA was made aware of the link between Permax and valve disease more than 5 years ago, when doctors at the Mayo Clinic reported in 2002, that 3 patients who had no history of heart disease had developed valve damage after taking Permax for several years and 2 had required replacement surgery to correct the problem.
This discovery led the doctors to review surgery records to determine whether any of the other 17 patients who had undergone valve replacement in the previous year had been taking pergolide and found that one other patient who required surgery had been on drug.
In 2004, as a follow-up to previous reports of valve disease, researchers led by Dr Richard Dewey Jr, an associate professor from the University of Texas Southwestern Medical Center, sent 200 letters to Parkinson's patients who were known to be on Permax to determine whether the earlier reports of valve damage were isolated cases.
For this study, echocardiograms were performed on 46 patients, and then compared to the results of a similar-aged healthy comparison group. The researchers determined that 89% of the Permax patients had evidence of leaky heart valves, and were up to 18 times more likely to have significant leakage in at least one valve than patients in the control group.
After the study was released, on April 28, 2004, HealthDay News reported that Dr Dewey recommended that Permax should be taken off the market back then.
In the two new studies in the New England Journal of Medicine, researchers note that the number of patients who developed heart valve damage is higher than previously expected.
One study conducted in Milan, Italy, titled, “Dopamine Agonists and the Risk of Cardiac-Valve Regurgitation,” led by Dr Renzo Zanettini, obtained records of echocardiograms for 155 patients taking the Parkinson’s drugs, and compared them to the records of 90 healthy patients in another group.
After analyzing the records, the researchers found moderate to severe valve damage in more than 23% of the Permax patients and 29% of Dostinex patients compared to less than 6% of the patients in the comparison group.
The second study, conducted by Dr Rene Schade and colleagues in Berlin and Montreal, analyzed records from more than 11,400 patients in Great Britain, between the ages of 40 to 80 who were prescribed the drugs between 1988 and 2005, and determined that Permax patients were 7 times more likely to have leaky heart valves and Dostinex patients were 5 times more likely to have valve damage, when compared to patients in the control group.
This second study also showed that Permax patients on the highest doses of the drug had a 37 times greater risk of developing valve disease, and at higher doses, Dostinex patients were over 50 times more likely to develop damage.
Dr Bryan Roth, a professor at the University of North Carolina School of Medicine and director of the psychoactive drug screening program at the National Institute of Mental Health, wrote an analysis that accompanied the studies in the NEJM, and said the drugs cause the same valve damage as Wyeth's fen-phen diet drugs that were pulled off the market in 1997.
According to Dr Roth, the drugs cause cells in the valves to multiply and thicken until the valves can no longer open and close properly. "The incidence is kind of mind-blowing," he told the Wall Street Journal on January 4, 2007.
"It's so prevalent in people taking these medications," he said, "you kind of wonder why it was missed."
Medical experts are not advising all patients who have taken these drugs to undergo testing to determine whether they have developed heart valve disease.
On March 29, 2006, the FDA withdrew Permax (pergolide) from the market because it increases the risk of valvular heart disease. Permax belongs to a class of drugs known as dopamine agonists that help regulate balance and movement in Parkinson's patients who suffer from a lack of dopamine.
When Permax was FDA approved in 1988, Eli Lilly marketed the drug, but in the US today, the drug is manufactured by Valeant Pharmaceuticals and generic versions are sold by Par and Teva. According to IMS Health, a prescription drug tracking firm, more than 72,000 prescriptions for the drug were written in 2006.
The decision by the FDA to take Permax off the market came after 2 recent studies were published in the New England Journal of Medicine in January 2007, that confirmed previous studies that linked Permax, and another drug prescribed to treat Parkinson's disease, Dostinex, to heart valve disease.
Dostinex is marketed by Pfizer, and is approved to treat Parkinson's patients in other countries. However, the drug has only been approved to treat the hormonal disorder, hyperprolactinemiam in the US, which means any prescriptions for Dostinex written for Parkinson's patients in this country were off-label, because the drug has never passed the required FDA approval process to demonstrate that it is safe and effective in treating patient's with Parkinson's disease.
The NEJM studies did not assess patients who were taking Dostinex for the hormonal disorder, and according to Dr Shlomo Melmed, an endocrinologist and a senior vice president of Cedars-Sinai Medical Center in Los Angeles, in the January 4, 2007, New York Times, tens of thousands of people in the US, mostly women, have taken the drug for hyperprolactinemiam.
Experts say the valve damage is not likely to be profound in patients treated for the hormone disorder because lower doses of Dostinex are used compared to Parkinson's patients, but Dr Melmed told the Times that men can develop the condition and may need higher doses, so those men should be monitored for heart valve damage.
In 2003, Eli Lilly first added the risk of heart valve damage to the Permax label but by then an estimated half million people had already taken the drug. Although the warning stated: "Some patients have required valve replacement, and deaths have been reported," Lilly said at the time that only 5 out of 100,000 patients developed valve damage.
The company also sent out a Dear Dr letter to prescribing doctors to warn about the increased risk in 2003, but the FDA did not add a black box warning about valve damage to the label on Permax until 2006. A "precaution" was also added to the label of Dostinex in December 2006.
Heart valve damage is a life-threatening condition that can lead to heart failure and sudden death. It cannot be treated with medication and open heart surgery for valve replacement is the only option available for patients with valve disease.
The surgery itself is complex, costly, and life-threatening. According to the Texas Heart Institute, for valve replacement surgery, the breastbone must be divided, the heart stopped, and blood must filtered through a heart-lung machine.
Following surgery, the Institute says, patients must be maintained in the Intensive Care Unit for one to 3 days, and patients typically remain hospitalized for about a week.
There are 2 types of valves used for replacement. Mechanical valves, which are made with plastic or metal, and biological valves which are made with animal tissue or human tissue from a donated heart.
Experts say, mechanical valves last longer than biological valves but blood tends to stick to devices, causing blood clots to form and patients often need to take a blood-thinning drug for life. Because blood thinners are known to increase the risk of bleeding within the body, patients taking the drugs must wear a medical alert bracelet at all times so medical professionals will know they are on the medication.
Patients with biological valves are usually not required to take blood-thinners but these valves are not as sturdy as the mechanical valves and often need to be replaced every 10 years.
According to FDA officials, to date the agency is aware of at least 14 cases where patients have required replacement surgery, but Dr Robert Temple of the FDA's office of drug evaluation, said at a briefing that 14 is likely to be an underestimate.
The FDA has consistently acknowledged on may occasions that only between 1% and 10% of all adverse events associated with prescription drugs are reported through the agency's data tracking system which means the actual number of patients with valve damage is bound to be much higher.
The FDA was made aware of the link between Permax and valve disease more than 5 years ago, when doctors at the Mayo Clinic reported in 2002, that 3 patients who had no history of heart disease had developed valve damage after taking Permax for several years and 2 had required replacement surgery to correct the problem.
This discovery led the doctors to review surgery records to determine whether any of the other 17 patients who had undergone valve replacement in the previous year had been taking pergolide and found that one other patient who required surgery had been on drug.
In 2004, as a follow-up to previous reports of valve disease, researchers led by Dr Richard Dewey Jr, an associate professor from the University of Texas Southwestern Medical Center, sent 200 letters to Parkinson's patients who were known to be on Permax to determine whether the earlier reports of valve damage were isolated cases.
For this study, echocardiograms were performed on 46 patients, and then compared to the results of a similar-aged healthy comparison group. The researchers determined that 89% of the Permax patients had evidence of leaky heart valves, and were up to 18 times more likely to have significant leakage in at least one valve than patients in the control group.
After the study was released, on April 28, 2004, HealthDay News reported that Dr Dewey recommended that Permax should be taken off the market back then.
In the two new studies in the New England Journal of Medicine, researchers note that the number of patients who developed heart valve damage is higher than previously expected.
One study conducted in Milan, Italy, titled, “Dopamine Agonists and the Risk of Cardiac-Valve Regurgitation,” led by Dr Renzo Zanettini, obtained records of echocardiograms for 155 patients taking the Parkinson’s drugs, and compared them to the records of 90 healthy patients in another group.
After analyzing the records, the researchers found moderate to severe valve damage in more than 23% of the Permax patients and 29% of Dostinex patients compared to less than 6% of the patients in the comparison group.
The second study, conducted by Dr Rene Schade and colleagues in Berlin and Montreal, analyzed records from more than 11,400 patients in Great Britain, between the ages of 40 to 80 who were prescribed the drugs between 1988 and 2005, and determined that Permax patients were 7 times more likely to have leaky heart valves and Dostinex patients were 5 times more likely to have valve damage, when compared to patients in the control group.
This second study also showed that Permax patients on the highest doses of the drug had a 37 times greater risk of developing valve disease, and at higher doses, Dostinex patients were over 50 times more likely to develop damage.
Dr Bryan Roth, a professor at the University of North Carolina School of Medicine and director of the psychoactive drug screening program at the National Institute of Mental Health, wrote an analysis that accompanied the studies in the NEJM, and said the drugs cause the same valve damage as Wyeth's fen-phen diet drugs that were pulled off the market in 1997.
According to Dr Roth, the drugs cause cells in the valves to multiply and thicken until the valves can no longer open and close properly. "The incidence is kind of mind-blowing," he told the Wall Street Journal on January 4, 2007.
"It's so prevalent in people taking these medications," he said, "you kind of wonder why it was missed."
Medical experts are not advising all patients who have taken these drugs to undergo testing to determine whether they have developed heart valve disease.
Thursday, July 29, 2010
Bush-Controlled FDA Moonlights as Big Pharma Pusher
Evelyn Pringle July 18, 2007
Americans need to stop and consider how many consumers will be killed and injured by dangerous drugs by the time George Bush heads back to Texas at the end of his Presidency, as a direct result of his allowing the interests of the pharmaceutical industry to take control of the FDA.
For nearly 70 years, the common-law tort systems in the individual states have provided a remedy for citizens injured by prescription drugs. However, in one of the most blatant paybacks for political contributions in US history, in January 2006, Bush-appointed officials at the FDA announced that the agency's approval of a drug and its labeling acts to preempt product liability lawsuits filed by patients against the pharmaceutical giants.
On February 23, 2006, Democratic lawmakers Rep Henry Waxman, of the Committee on Government Reform, and Reps John Dingell and Sherrod Brown of the Committee on Energy and Commerce, sent a letter to the Secretary of Health and Human Services, and voiced their outrage.
"The announcement," the lawmakers wrote, "provides unfortunate evidence that the Bush Administration is more committed to protecting drug industry profits than to building a sound system for ensuring drug safety."
"The FDA's preemption announcement," the letter said, "is particularly troubling at a time when FDA's own ability to protect Americans from unsafe drugs has been called into question by a series of cases in which the FDA was slow to warn consumers of significant drug risks."
The new rules went into effect on June 30, 2006, and preemption is now being used in litigation all over the country in an attempt to dismiss lawsuits filed by private citizens against drug companies.
Unbeknownst to average Americans, the administration's gift of preemption is not limited to industries regulated by the FDA. Bush-appointed officials in all federal regulatory agencies are working in concert to ensure that major corporations subject to product liability lawsuits can claim that federal regulation of their products preempts any recovery for consumers harmed, whether the injury involves defective automobiles, pesticides or whatever.
In return, the major corporations are ganging up on private citizens by filing amicus briefs in support of pharmaceutical companies involved in litigation. For instance, the drug giant Wyeth is arguing preemption in a petition currently pending before the US Supreme Court in a case involving one lone woman in Vermont, in an attempt to overturn a jury verdict that was affirmed by the Vermont Supreme Court.
Amicus briefs to support Wyeth's preemption argument are piling up, including one filed by the Product Liability Advisory Council on behalf of just about every major product manufacturer in America.
The plaintiff, Diana Levine, a professional musician, has the support of the Public Citizen Litigation Group. Ms Levine went to the hospital to seek treatment for a headache and left with injuries that led to the amputation of her arm after the drug Phenergan was administered by IV to alleviate the nausea associated with a migraine headache.
Specifically, her arm had to be amputated because the drug reached Ms Levine's arteries, and the lawsuit alleges that Wyeth was aware of the risk of arterial contact when the drug was administered by IV and failed to warn against using a method to administer Phenergan that caused the injury.
In the petition, Wyeth does not dispute that Ms Levine's arm was amputated because the company failed to warn about using this method. Its sole argument is that she is not entitled to damages because the FDA did not require Wyeth to warn about the danger of administering the drug this way.
The Vermont Supreme Court rejected this argument. The agency's claim of conflict with federal law, the Court held, did not warrant deference because it was flatly at odds with both the FDA's regulation permitting manufacturers "to add or strengthen a warning 'to increase the safe use of the drug product' without prior FDA approval," and with Congress' express directive that state law concerning prescription drugs be superseded only when it poses a '"direct and positive conflict' with federal law."
On May 21, 2007, the Supreme Court invited the Solicitor General to file a brief to express the views of the government, which will no doubt add support for a favorable preemption ruling for Wyeth, potentially affecting tens of thousand of private citizens with cases pending all over the country.
A favorable ruling on preemption could provide an escape hatch for GlaxoSmithKline in lawsuits filed by patients injured by the diabetes drug Avandia (rosiglitazone), even though the FDA is aware of the fact that Glaxo concealed the serious cardiovascular risks known to be associated with the drug for years.
Medical experts are now predicting another Vioxx-like disaster with Avandia. In May 2007, prominent cardiologist Dr Steven Nissen, of the Cleveland Clinic, reported a study in the New England Journal of Medicine that found the drug to be associated with a 43% increase in heart attacks and possibly a 64% increase in cardiovascular death.
In a May 26, 2007, speech on the Senate Floor, Senator Charles Grassley (R-Iowa) said that the actual number of heart attacks possibly linked to Avandia may be as high as 20 a day.
Since the drug came on the market about 8 years ago, he said, tens of millions of prescriptions have been written, and Medicare and Medicaid have paid hundreds of millions of dollars for the drug.
At a June 6, 2007, hearing of the House Committee on Oversight and Government Reform to review the FDA's failure to warn the public about Avandia, Chairman Waxman (D-Cal) began the meeting by pointing out: "It is not Congress' role to adjudicate these medical issues."
"But it is our role," he noted, "to ensure that the Food and Drug Administration is taking these concerns seriously and providing doctors and patients with the guidance they need to make informed decisions."
"Although Avandia has been on the market for eight years and has been used by millions of Americans," Rep Waxman said, "the post-market studies have not been done to say conclusively whether Avandia increases or decreases the risk of heart attacks."
"That's a major failure of our system," he said. "And it is what is causing so much confusion and worry among the patients who are taking Avandia today."
Another FDA failure that will surely lead to many lawsuits was allowing Permax (pergolide), a drug used by Parkinson's patients, to remain on the market until March 29, 2007, long after its link to valvular heart damage was known.
Eli Lilly gained approval for Permax in 1988 but, at the time of the recall, the drug was manufactured by Valeant Pharmaceuticals and generics were sold by Par and Teva.
As early as December 2002, doctors at the Mayo Clinic reported that 3 Permax patients had developed heart valve disease similar to that caused by the Fen-Phen diet combination.
In 2004, HealthDay News reported that a study had confirmed earlier findings that Permax was linked to heart valve damage which required surgery to correct.
On January 4, 2007, two studies in the New England Journal of Medicine said that the number of patients developing valve damage was higher than expected. One study found moderate to severe valve problems in more than 23% of the patients on Permax, compared to less than 6% in the comparison group.
The second study found Permax users were 5 to 7 times more likely to have leaky heart valves than patients taking other Parkinson's drugs, and patients taking the highest doses of Permax were at a 37 times greater risk.
The FDA's preemption policy has the potential to benefit every major drug company. Johnson & Johnson's SEC filings show that the company is currently facing hundreds of lawsuits over the deaths and injuries linked to the Ortho Evra birth control patch in women all over the country who have suffered blood clots, heart attacks and strokes.
Legal analysts predict that many more lawsuits will be filed due to the wide use of the device and as women realize that their injuries are due to the patch. In 2005 alone, there were more than 9.4 million prescriptions issued for the Ortho Evra patch, according to IMS Health, an industry-tracking firm.
A preemption ruling in this litigation would be especially onerous in light of the fact that the injuries are clearly due to the patch, because blood clots, heart attacks and stroke are almost unheard of in the age group of women who use this device.
This is another case where FDA officials knew of the health risks before the drug was approved. Agency records show that in 2000, the FDA scientist in charge of reviewing the preapproval trials submitted, warned that blood clots could occur and recommended that the information be included in the prescribing information for the patch.
The new drug application for the antibiotic, Ketek, marketed by Sanofi-Aventis, was rejected twice, in 2001 and 2003, before FDA management approved the drug on April 1, 2004, based on fraudulent studies, and over the objections of the FDA's own scientists.
Many patients have been harmed because doctors trusted the FDA's approval of Ketek. According to a review of the FDA's Adverse Event Reporting System, by the staff of the Senate Finance Committee, between July 2005 and September 2005 alone, there were two deaths, 35 liver adverse reactions, 44 cardiac events, and 80 visual events in Ketek patients.
In addition, internal FDA emails obtained by staffers, prove that top FDA officials were aware of the problems with Ketek before it was approved, and that FDA scientists, Dr David Ross, Dr David Graham, Dr Charles Cooper, and Dr Rosemary Johann-Liang, all warned FDA management about the serious adverse effects associated with the drug.
A May 16, 2006, FDA memo authored by safety reviewers said Ketek was linked to 12 reported liver failures including 4 deaths, 23 reports of serious liver injury, and a higher rate of adverse reaction reports than other antibiotics on the market, and the reviewers recommended a black box warning for the Ketek-related liver injury.
However, Sanofi-Aventis and FDA officials disregarded the recommendation and announced that only a new bolded warning would be added.
In addition to the massive Vioxx litigation, Merck is facing a large number of plaintiffs in lawsuits over the osteoporosis drug Fosamax, alleging the drug causes jaw-bone death, which is an extremely rare condition.
Kenneth Hargreaves of the University of Texas, discussed the increasing cases of OJN in the April 3, 2006 LA Times. "We've uncovered about 1,000 patients in the past six to nine months alone," he said, "so the magnitude of the problem is just starting to be recognized."
Oral surgeon, Dr Salvatore Ruggiero, one of the first doctors to notice the increase in 2001, told the Times, "Even though the chances of getting this are small, considering there are 23 million women taking this drug, we could be talking about a significant number of people."
The FDA approved Fosamax in 1995, and because it is a relatively new drug, unreported cases OJN may be higher than expected because doctors may attribute the pain caused by the condition to osteoporosis, according to Diane Wysowski of the FDA's Office of Drug Safety in the Times.
Here again, the FDA and the drug maker were aware of the link between OJN and Fosamax but failed to warn the public until after the drug was prescribed to tens of millions of patients.
The man most credited for the creation of the preemption policy is the FDA's former Chief Counsel, Daniel Troy, who plays for the opposite team in private practice. Prior to his appointment as Chief Counsel, Mr Troy was a partner at Washington's Wiley Rein & Fielding, where he filed lawsuits against the FDA on behalf of the pharmaceutical industry to loosen restrictions on off-label prescribing and advertising of prescription drugs.
In fact, critics say, it was Mr Troy's loyalty to the industry, demonstrated by years of legal battles against FDA regulations, that earned him the appointment by the Bush administration as the industry's inside legal counsel.
Mr Troy himself bragged about his part in implementing the preemption policy in an article he wrote in the October 9, 2006, Legal Times stating: "I was also at the FDA while January's Physician Labeling Rule, which contains a statement in its preamble about the FDA's pre-emption authority, was written."
"And I now," Mr Troy states, "advise and represent companies confronting state-law claims that implicate the pre-emptive effect of FDA requirements."
But the fact is, Mr Troy was testing the viability of the preemption argument with judges in state and federal courts long before the new policy was announced in January 2006, by filing amicus briefs on behalf of drug companies and against private citizens in cases involving the new class of selective serotonin reuptake inhibitor antidepressants (SSRI's) back in 2002.
Critics say it's a toss-up between Vioxx and the SSRI's when it comes to the number of deaths and injuries that could have been prevented if the information about the serious health risks known to the drug makers had not been concealed.
Over the last 2 decades, SSRI's, which include Paxil, Zoloft, Prozac, Celexa, Luvox and Lexapro, have been prescribed off-label for uses not approved by the FDA more often than any other drugs in history. The Journal of Clinical Psychiatry found that 75% of SSRI prescriptions were written for unapproved uses in June 2005.
Critics say that the profits that have resulted from the massive off-label use of SSRI's, and especially with children, are a direct result of their illegal promotion by the drug makers.
The success of the off-label marketing of SSRI's is evidenced by a June 29, 2007, report by Reuters that found the most commonly prescribed drugs in the US are antidepressants.
While most of the focus has remained on the risk of suicide, SSRI's have also been linked to extreme violence, including homicides, several life-threatening birth defects, abnormal uterine or gastrointestinal bleeding, a decrease in bone mineral density, sexual dysfunction, fertility problems and a severe withdrawal syndrome.
In September 2002, Mr Troy filed the FDA's first brief in support of preemption in the Zoloft suicide case of Motus v Pfizer, based on a request by Pfizer attorney Malcolm Wheeler. In the brief, Mr Troy claimed that warnings of a causal relationship between Zoloft and suicide would have misbranded the drug and that "any warning, no matter how worded, that could reasonably have been read as describing or alluding to such a relation would have been false or misleading, and therefore in conflict with federal law."
Baum Hedlund partner, Attorney Karen Barth Menzies, has been battling the SSRI makers in the legal arena for more than a decade in representing plaintiffs with claims involving Prozac, Paxil and Zoloft.
Ms Menzies says Mr Troy's argument is absurd because Wyeth strengthened the warning about suicidality on the label of Effexor in August 2003, without obtaining prior FDA approval, and the FDA did not sanction Wyeth or claim the label was false and misleading.
Ms Menzies has defeated the preemption arguments by Mr Troy offered in support of Pfizer and GlaxoSmithKline in a number of cases. The court never reached the preemption issue in Motus because the case was resolved on other grounds, but in September 2002, Mr Troy tried to use the same argument in a lawsuit that alleged Glaxo had failed to warn about the withdrawal effects of Paxil, and the judge stated the argument "contravenes common sense" and "vitiates, rather than advances, the purpose of protecting the public."
Pfizer also submitted Mr Troy's brief from Motus to support a preemption in the case of Witczak v Pfizer. In rejecting the argument, the court pointed out that: "State consumer-protection law compliments, rather than frustrates, the FDA's protective regime."
"This is especially apparent," the court said, "when one considers that prescription drugs were once marketed primarily to trained health care providers -- sophisticated and discerning intermediaries."
"Today, on the other hand, pill-rolling apothecaries and the mortar and pestle have disappeared," he stated. "They have been replaced by drug manufacturers who urge the use of their drugs in mass-market print and television advertisements targeted directly at the public," he said.
As an example, the judge noted that Glaxo had advertised the drug Paxil, "by personifying it as a happy, bouncing-oval cartoon character."
After effectively allocating the power of FDA to drug companies, in 2004, Mr Troy went back to representing the pharmaceutical industry with the preemption policy tucked in his back pocket.
But his departure did not stop Pfizer from trying to use the FDA preemption argument in the Zoloft suicide case of Cartwright v Pfizer, decided in 2005, in which the court rejected Pfizer's preemption argument, finding that Texas tort law "compliments and is parallel to the FDA's regulations regarding safety warnings and, thus, does not interfere with the objectives of the FDA."
The court further noted that the FDA mandates that "manufacturer[s] issue a warning whenever there is 'reasonable evidence of an association of a serious hazard with a drug; a causal relationship need not have been proved.'"
The truth is that the FDA knew about the risk of suicidality in children taking Zoloft, because the agency's review of Pfizer’s clinical trial data in 1996 showed the risk to be five times that of adults on Zoloft and caused enough concern that FDA reviewer Dr James Knudsen wrote to Pfizer asking for an explanation.
The FDA's new preemption policy also purports to immunize doctors. "Pre-emption would include not only claims against manufacturers," the FDA states, "but also against health-care practitioners for claims related to dissemination of risk information to patients beyond what is included in the labeling."
Critics say this language is absurd because it extends protection to all the doctors who are boosting sales for the drug makers by prescribing drugs off-label, and the FDA labeling carries no prescribing information for an unapproved use and no warnings about the risks that may be associated with a drug in treating patients for an off-label condition.
"The unqualified language of this statement," Mr Waxman's letter states, "would appear to preempt cases against physicians for failure to warn a patient of risks associated with an off-label (unapproved) use, since, by definition, such risks rarely appear in the approved drug label."
However, drug companies have been immunizing doctors who prescribe their drugs off-label for years. For instance, in Eli Lilly's first out-of-court settlement with 8,000 plaintiffs in litigation involving the off-label marketing of the antipsychotic Zyprexa in late 2004, the settlement agreement included a ban on suing the doctors who prescribed Zyprexa off-label, according to a plaintiff involved in the case.
A July 7, 2003, Lilly document entitled, "Diabetes Update," recently made public as a result of litigation, describes a plan to immunize doctors so they would continue to prescribe Zyprexa off-label when Lilly learned that the warning about high blood sugar levels and diabetes was about to be announced by the FDA and the American Diabetes Association.
"We must embrace the fact that many physicians are curtailing their use of Zyprexa (particularly in the moderately-ill patient and in the maintenance phase)," the Lilly memo states, "solely on the basis of personal fear (of being sued)."
"Indemnification," the document notes, "represents the most meaningful demonstration of confidence in Zyprexa--both with our customers and with our employees."
The memo brags about the success of the scheme when used with doctors prescribing the company's SSRI. "Our experience with Prozac," it states, "confirms the impact and goodwill of such an initiative."
The drug makers are well aware that the steady flow of profits from off-label marketing schemes would come to a screeching halt without the participation of the prescribing doctors. However, the termination date for the immunization coverage extended to the doctors prescribing Zyprexa by Eli Lilly or the FDA is right around the corner, because the fraudulent billings that have resulted from off-label prescribing of the new class of antipsychotics are bankrupting state Medicaid programs all over the US.
Also, state officials are zeroing in on the money paid to the prescribing doctors. On June 26, in the New York Times, Gardiner Harris reported that states are finding that psychiatrists earn more money from drug companies than doctors in any other specialty, and the psychiatrists who receive the most money from antipsychotic makers prescribe antipsychotics like Zyprexa to children most often.
In the Times, Mr Harris noted that Vermont officials reported that drug company payments to Vermont psychiatrists more than doubled last year, from an average of $20,835 in 2005, up to $45,692 in 2006, and that antipsychotics were among the largest expenses for the Vermont Medicaid program.
He also reported a similar pattern in Minnesota where psychiatrists earned the most money, with payments ranging from $51 to $689,000, and the psychiatrists who took the most money from the makers of antipsychotics prescribed the drugs to children most often.
The atypical antipsychotic makers are currently under investigation by congressional committees and federal and state law enforcement agencies for defrauding public health care programs by marketing the drugs off-label to kids as young as toddlers, as well as elderly citizens in nursing homes, and causing serious injury and death to many patients.
However, Lilly recently purchased a new insurance policy of sorts to keep federal regulators at bay, in hiring Alex Azar II, the former Deputy Secretary of the US Health and Human Services Department, who quit his government job in February 2007 and became a senior vice president at Lilly in May 2007.
According to Lilly's press release, Mr Azar formerly supervised all operations at the HHS, and one of the agencies under his direction was the FDA.
When considering the tens of thousands of lawsuits that have been filed by plaintiffs injured by the new antipsychotics, a favorable ruling on preemption could be worth billions of dollars to the drug makers.
Written as part of a series on Avandia sponsored by Baum, Hedlund, Aristei, Goldman & Menzies’ Pharmaceutical Litigation Department
Americans need to stop and consider how many consumers will be killed and injured by dangerous drugs by the time George Bush heads back to Texas at the end of his Presidency, as a direct result of his allowing the interests of the pharmaceutical industry to take control of the FDA.
For nearly 70 years, the common-law tort systems in the individual states have provided a remedy for citizens injured by prescription drugs. However, in one of the most blatant paybacks for political contributions in US history, in January 2006, Bush-appointed officials at the FDA announced that the agency's approval of a drug and its labeling acts to preempt product liability lawsuits filed by patients against the pharmaceutical giants.
On February 23, 2006, Democratic lawmakers Rep Henry Waxman, of the Committee on Government Reform, and Reps John Dingell and Sherrod Brown of the Committee on Energy and Commerce, sent a letter to the Secretary of Health and Human Services, and voiced their outrage.
"The announcement," the lawmakers wrote, "provides unfortunate evidence that the Bush Administration is more committed to protecting drug industry profits than to building a sound system for ensuring drug safety."
"The FDA's preemption announcement," the letter said, "is particularly troubling at a time when FDA's own ability to protect Americans from unsafe drugs has been called into question by a series of cases in which the FDA was slow to warn consumers of significant drug risks."
The new rules went into effect on June 30, 2006, and preemption is now being used in litigation all over the country in an attempt to dismiss lawsuits filed by private citizens against drug companies.
Unbeknownst to average Americans, the administration's gift of preemption is not limited to industries regulated by the FDA. Bush-appointed officials in all federal regulatory agencies are working in concert to ensure that major corporations subject to product liability lawsuits can claim that federal regulation of their products preempts any recovery for consumers harmed, whether the injury involves defective automobiles, pesticides or whatever.
In return, the major corporations are ganging up on private citizens by filing amicus briefs in support of pharmaceutical companies involved in litigation. For instance, the drug giant Wyeth is arguing preemption in a petition currently pending before the US Supreme Court in a case involving one lone woman in Vermont, in an attempt to overturn a jury verdict that was affirmed by the Vermont Supreme Court.
Amicus briefs to support Wyeth's preemption argument are piling up, including one filed by the Product Liability Advisory Council on behalf of just about every major product manufacturer in America.
The plaintiff, Diana Levine, a professional musician, has the support of the Public Citizen Litigation Group. Ms Levine went to the hospital to seek treatment for a headache and left with injuries that led to the amputation of her arm after the drug Phenergan was administered by IV to alleviate the nausea associated with a migraine headache.
Specifically, her arm had to be amputated because the drug reached Ms Levine's arteries, and the lawsuit alleges that Wyeth was aware of the risk of arterial contact when the drug was administered by IV and failed to warn against using a method to administer Phenergan that caused the injury.
In the petition, Wyeth does not dispute that Ms Levine's arm was amputated because the company failed to warn about using this method. Its sole argument is that she is not entitled to damages because the FDA did not require Wyeth to warn about the danger of administering the drug this way.
The Vermont Supreme Court rejected this argument. The agency's claim of conflict with federal law, the Court held, did not warrant deference because it was flatly at odds with both the FDA's regulation permitting manufacturers "to add or strengthen a warning 'to increase the safe use of the drug product' without prior FDA approval," and with Congress' express directive that state law concerning prescription drugs be superseded only when it poses a '"direct and positive conflict' with federal law."
On May 21, 2007, the Supreme Court invited the Solicitor General to file a brief to express the views of the government, which will no doubt add support for a favorable preemption ruling for Wyeth, potentially affecting tens of thousand of private citizens with cases pending all over the country.
A favorable ruling on preemption could provide an escape hatch for GlaxoSmithKline in lawsuits filed by patients injured by the diabetes drug Avandia (rosiglitazone), even though the FDA is aware of the fact that Glaxo concealed the serious cardiovascular risks known to be associated with the drug for years.
Medical experts are now predicting another Vioxx-like disaster with Avandia. In May 2007, prominent cardiologist Dr Steven Nissen, of the Cleveland Clinic, reported a study in the New England Journal of Medicine that found the drug to be associated with a 43% increase in heart attacks and possibly a 64% increase in cardiovascular death.
In a May 26, 2007, speech on the Senate Floor, Senator Charles Grassley (R-Iowa) said that the actual number of heart attacks possibly linked to Avandia may be as high as 20 a day.
Since the drug came on the market about 8 years ago, he said, tens of millions of prescriptions have been written, and Medicare and Medicaid have paid hundreds of millions of dollars for the drug.
At a June 6, 2007, hearing of the House Committee on Oversight and Government Reform to review the FDA's failure to warn the public about Avandia, Chairman Waxman (D-Cal) began the meeting by pointing out: "It is not Congress' role to adjudicate these medical issues."
"But it is our role," he noted, "to ensure that the Food and Drug Administration is taking these concerns seriously and providing doctors and patients with the guidance they need to make informed decisions."
"Although Avandia has been on the market for eight years and has been used by millions of Americans," Rep Waxman said, "the post-market studies have not been done to say conclusively whether Avandia increases or decreases the risk of heart attacks."
"That's a major failure of our system," he said. "And it is what is causing so much confusion and worry among the patients who are taking Avandia today."
Another FDA failure that will surely lead to many lawsuits was allowing Permax (pergolide), a drug used by Parkinson's patients, to remain on the market until March 29, 2007, long after its link to valvular heart damage was known.
Eli Lilly gained approval for Permax in 1988 but, at the time of the recall, the drug was manufactured by Valeant Pharmaceuticals and generics were sold by Par and Teva.
As early as December 2002, doctors at the Mayo Clinic reported that 3 Permax patients had developed heart valve disease similar to that caused by the Fen-Phen diet combination.
In 2004, HealthDay News reported that a study had confirmed earlier findings that Permax was linked to heart valve damage which required surgery to correct.
On January 4, 2007, two studies in the New England Journal of Medicine said that the number of patients developing valve damage was higher than expected. One study found moderate to severe valve problems in more than 23% of the patients on Permax, compared to less than 6% in the comparison group.
The second study found Permax users were 5 to 7 times more likely to have leaky heart valves than patients taking other Parkinson's drugs, and patients taking the highest doses of Permax were at a 37 times greater risk.
The FDA's preemption policy has the potential to benefit every major drug company. Johnson & Johnson's SEC filings show that the company is currently facing hundreds of lawsuits over the deaths and injuries linked to the Ortho Evra birth control patch in women all over the country who have suffered blood clots, heart attacks and strokes.
Legal analysts predict that many more lawsuits will be filed due to the wide use of the device and as women realize that their injuries are due to the patch. In 2005 alone, there were more than 9.4 million prescriptions issued for the Ortho Evra patch, according to IMS Health, an industry-tracking firm.
A preemption ruling in this litigation would be especially onerous in light of the fact that the injuries are clearly due to the patch, because blood clots, heart attacks and stroke are almost unheard of in the age group of women who use this device.
This is another case where FDA officials knew of the health risks before the drug was approved. Agency records show that in 2000, the FDA scientist in charge of reviewing the preapproval trials submitted, warned that blood clots could occur and recommended that the information be included in the prescribing information for the patch.
The new drug application for the antibiotic, Ketek, marketed by Sanofi-Aventis, was rejected twice, in 2001 and 2003, before FDA management approved the drug on April 1, 2004, based on fraudulent studies, and over the objections of the FDA's own scientists.
Many patients have been harmed because doctors trusted the FDA's approval of Ketek. According to a review of the FDA's Adverse Event Reporting System, by the staff of the Senate Finance Committee, between July 2005 and September 2005 alone, there were two deaths, 35 liver adverse reactions, 44 cardiac events, and 80 visual events in Ketek patients.
In addition, internal FDA emails obtained by staffers, prove that top FDA officials were aware of the problems with Ketek before it was approved, and that FDA scientists, Dr David Ross, Dr David Graham, Dr Charles Cooper, and Dr Rosemary Johann-Liang, all warned FDA management about the serious adverse effects associated with the drug.
A May 16, 2006, FDA memo authored by safety reviewers said Ketek was linked to 12 reported liver failures including 4 deaths, 23 reports of serious liver injury, and a higher rate of adverse reaction reports than other antibiotics on the market, and the reviewers recommended a black box warning for the Ketek-related liver injury.
However, Sanofi-Aventis and FDA officials disregarded the recommendation and announced that only a new bolded warning would be added.
In addition to the massive Vioxx litigation, Merck is facing a large number of plaintiffs in lawsuits over the osteoporosis drug Fosamax, alleging the drug causes jaw-bone death, which is an extremely rare condition.
Kenneth Hargreaves of the University of Texas, discussed the increasing cases of OJN in the April 3, 2006 LA Times. "We've uncovered about 1,000 patients in the past six to nine months alone," he said, "so the magnitude of the problem is just starting to be recognized."
Oral surgeon, Dr Salvatore Ruggiero, one of the first doctors to notice the increase in 2001, told the Times, "Even though the chances of getting this are small, considering there are 23 million women taking this drug, we could be talking about a significant number of people."
The FDA approved Fosamax in 1995, and because it is a relatively new drug, unreported cases OJN may be higher than expected because doctors may attribute the pain caused by the condition to osteoporosis, according to Diane Wysowski of the FDA's Office of Drug Safety in the Times.
Here again, the FDA and the drug maker were aware of the link between OJN and Fosamax but failed to warn the public until after the drug was prescribed to tens of millions of patients.
The man most credited for the creation of the preemption policy is the FDA's former Chief Counsel, Daniel Troy, who plays for the opposite team in private practice. Prior to his appointment as Chief Counsel, Mr Troy was a partner at Washington's Wiley Rein & Fielding, where he filed lawsuits against the FDA on behalf of the pharmaceutical industry to loosen restrictions on off-label prescribing and advertising of prescription drugs.
In fact, critics say, it was Mr Troy's loyalty to the industry, demonstrated by years of legal battles against FDA regulations, that earned him the appointment by the Bush administration as the industry's inside legal counsel.
Mr Troy himself bragged about his part in implementing the preemption policy in an article he wrote in the October 9, 2006, Legal Times stating: "I was also at the FDA while January's Physician Labeling Rule, which contains a statement in its preamble about the FDA's pre-emption authority, was written."
"And I now," Mr Troy states, "advise and represent companies confronting state-law claims that implicate the pre-emptive effect of FDA requirements."
But the fact is, Mr Troy was testing the viability of the preemption argument with judges in state and federal courts long before the new policy was announced in January 2006, by filing amicus briefs on behalf of drug companies and against private citizens in cases involving the new class of selective serotonin reuptake inhibitor antidepressants (SSRI's) back in 2002.
Critics say it's a toss-up between Vioxx and the SSRI's when it comes to the number of deaths and injuries that could have been prevented if the information about the serious health risks known to the drug makers had not been concealed.
Over the last 2 decades, SSRI's, which include Paxil, Zoloft, Prozac, Celexa, Luvox and Lexapro, have been prescribed off-label for uses not approved by the FDA more often than any other drugs in history. The Journal of Clinical Psychiatry found that 75% of SSRI prescriptions were written for unapproved uses in June 2005.
Critics say that the profits that have resulted from the massive off-label use of SSRI's, and especially with children, are a direct result of their illegal promotion by the drug makers.
The success of the off-label marketing of SSRI's is evidenced by a June 29, 2007, report by Reuters that found the most commonly prescribed drugs in the US are antidepressants.
While most of the focus has remained on the risk of suicide, SSRI's have also been linked to extreme violence, including homicides, several life-threatening birth defects, abnormal uterine or gastrointestinal bleeding, a decrease in bone mineral density, sexual dysfunction, fertility problems and a severe withdrawal syndrome.
In September 2002, Mr Troy filed the FDA's first brief in support of preemption in the Zoloft suicide case of Motus v Pfizer, based on a request by Pfizer attorney Malcolm Wheeler. In the brief, Mr Troy claimed that warnings of a causal relationship between Zoloft and suicide would have misbranded the drug and that "any warning, no matter how worded, that could reasonably have been read as describing or alluding to such a relation would have been false or misleading, and therefore in conflict with federal law."
Baum Hedlund partner, Attorney Karen Barth Menzies, has been battling the SSRI makers in the legal arena for more than a decade in representing plaintiffs with claims involving Prozac, Paxil and Zoloft.
Ms Menzies says Mr Troy's argument is absurd because Wyeth strengthened the warning about suicidality on the label of Effexor in August 2003, without obtaining prior FDA approval, and the FDA did not sanction Wyeth or claim the label was false and misleading.
Ms Menzies has defeated the preemption arguments by Mr Troy offered in support of Pfizer and GlaxoSmithKline in a number of cases. The court never reached the preemption issue in Motus because the case was resolved on other grounds, but in September 2002, Mr Troy tried to use the same argument in a lawsuit that alleged Glaxo had failed to warn about the withdrawal effects of Paxil, and the judge stated the argument "contravenes common sense" and "vitiates, rather than advances, the purpose of protecting the public."
Pfizer also submitted Mr Troy's brief from Motus to support a preemption in the case of Witczak v Pfizer. In rejecting the argument, the court pointed out that: "State consumer-protection law compliments, rather than frustrates, the FDA's protective regime."
"This is especially apparent," the court said, "when one considers that prescription drugs were once marketed primarily to trained health care providers -- sophisticated and discerning intermediaries."
"Today, on the other hand, pill-rolling apothecaries and the mortar and pestle have disappeared," he stated. "They have been replaced by drug manufacturers who urge the use of their drugs in mass-market print and television advertisements targeted directly at the public," he said.
As an example, the judge noted that Glaxo had advertised the drug Paxil, "by personifying it as a happy, bouncing-oval cartoon character."
After effectively allocating the power of FDA to drug companies, in 2004, Mr Troy went back to representing the pharmaceutical industry with the preemption policy tucked in his back pocket.
But his departure did not stop Pfizer from trying to use the FDA preemption argument in the Zoloft suicide case of Cartwright v Pfizer, decided in 2005, in which the court rejected Pfizer's preemption argument, finding that Texas tort law "compliments and is parallel to the FDA's regulations regarding safety warnings and, thus, does not interfere with the objectives of the FDA."
The court further noted that the FDA mandates that "manufacturer[s] issue a warning whenever there is 'reasonable evidence of an association of a serious hazard with a drug; a causal relationship need not have been proved.'"
The truth is that the FDA knew about the risk of suicidality in children taking Zoloft, because the agency's review of Pfizer’s clinical trial data in 1996 showed the risk to be five times that of adults on Zoloft and caused enough concern that FDA reviewer Dr James Knudsen wrote to Pfizer asking for an explanation.
The FDA's new preemption policy also purports to immunize doctors. "Pre-emption would include not only claims against manufacturers," the FDA states, "but also against health-care practitioners for claims related to dissemination of risk information to patients beyond what is included in the labeling."
Critics say this language is absurd because it extends protection to all the doctors who are boosting sales for the drug makers by prescribing drugs off-label, and the FDA labeling carries no prescribing information for an unapproved use and no warnings about the risks that may be associated with a drug in treating patients for an off-label condition.
"The unqualified language of this statement," Mr Waxman's letter states, "would appear to preempt cases against physicians for failure to warn a patient of risks associated with an off-label (unapproved) use, since, by definition, such risks rarely appear in the approved drug label."
However, drug companies have been immunizing doctors who prescribe their drugs off-label for years. For instance, in Eli Lilly's first out-of-court settlement with 8,000 plaintiffs in litigation involving the off-label marketing of the antipsychotic Zyprexa in late 2004, the settlement agreement included a ban on suing the doctors who prescribed Zyprexa off-label, according to a plaintiff involved in the case.
A July 7, 2003, Lilly document entitled, "Diabetes Update," recently made public as a result of litigation, describes a plan to immunize doctors so they would continue to prescribe Zyprexa off-label when Lilly learned that the warning about high blood sugar levels and diabetes was about to be announced by the FDA and the American Diabetes Association.
"We must embrace the fact that many physicians are curtailing their use of Zyprexa (particularly in the moderately-ill patient and in the maintenance phase)," the Lilly memo states, "solely on the basis of personal fear (of being sued)."
"Indemnification," the document notes, "represents the most meaningful demonstration of confidence in Zyprexa--both with our customers and with our employees."
The memo brags about the success of the scheme when used with doctors prescribing the company's SSRI. "Our experience with Prozac," it states, "confirms the impact and goodwill of such an initiative."
The drug makers are well aware that the steady flow of profits from off-label marketing schemes would come to a screeching halt without the participation of the prescribing doctors. However, the termination date for the immunization coverage extended to the doctors prescribing Zyprexa by Eli Lilly or the FDA is right around the corner, because the fraudulent billings that have resulted from off-label prescribing of the new class of antipsychotics are bankrupting state Medicaid programs all over the US.
Also, state officials are zeroing in on the money paid to the prescribing doctors. On June 26, in the New York Times, Gardiner Harris reported that states are finding that psychiatrists earn more money from drug companies than doctors in any other specialty, and the psychiatrists who receive the most money from antipsychotic makers prescribe antipsychotics like Zyprexa to children most often.
In the Times, Mr Harris noted that Vermont officials reported that drug company payments to Vermont psychiatrists more than doubled last year, from an average of $20,835 in 2005, up to $45,692 in 2006, and that antipsychotics were among the largest expenses for the Vermont Medicaid program.
He also reported a similar pattern in Minnesota where psychiatrists earned the most money, with payments ranging from $51 to $689,000, and the psychiatrists who took the most money from the makers of antipsychotics prescribed the drugs to children most often.
The atypical antipsychotic makers are currently under investigation by congressional committees and federal and state law enforcement agencies for defrauding public health care programs by marketing the drugs off-label to kids as young as toddlers, as well as elderly citizens in nursing homes, and causing serious injury and death to many patients.
However, Lilly recently purchased a new insurance policy of sorts to keep federal regulators at bay, in hiring Alex Azar II, the former Deputy Secretary of the US Health and Human Services Department, who quit his government job in February 2007 and became a senior vice president at Lilly in May 2007.
According to Lilly's press release, Mr Azar formerly supervised all operations at the HHS, and one of the agencies under his direction was the FDA.
When considering the tens of thousands of lawsuits that have been filed by plaintiffs injured by the new antipsychotics, a favorable ruling on preemption could be worth billions of dollars to the drug makers.
Written as part of a series on Avandia sponsored by Baum, Hedlund, Aristei, Goldman & Menzies’ Pharmaceutical Litigation Department
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