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The U.S. Food & Drug Administration in association with The Center for Drug Evaluation and Research has released a podcast regarding the recent Permax Recall.

The information contained in the podcast is very informative.  

We’d like to commend the FDA for making this type of valuable information available to the American public.  It not only helps the average consumer but also those people with visual disabilities that must utilize screen readers, etc.  Nice work FDA!

Source | FDA / CDER

Run Time — 6:32 minutes

>>> CLICK HERE TO LISTEN TO PERMAX RECALL PODCAST <<<

Full Transcript Below

[music]

On March 29, 2007, the Food and Drug Administration issued a Public Health Advisory titled: Voluntary Market Withdrawal of Permax.

The drug is also known and marketed by its generic name pergolide [per-go-lide].

I am Pat Clarke from F-D-A’s Center for Drug Evaluation and Research.

We are notifying you that the companies that manufacture and distribute pergolide have agreed to withdraw this drug from the market due to the potential for heart valve damage.

Two new studies showed that patients with Parkinson’s disease who were treated with pergolide had an increased chance of serious damage to their heart valves when compared to patients who did not receive the drug.

Pergolide is a member of a class of drugs known as dopamine [dough-pah-mean] agonists and is used with levodopa and carbidopa to manage the signs and symptoms of Parkinson’s disease, which include tremors and slowness of movement.

If you are a patient with Parkinson’s disease who is taking pergolide, you should take these two steps:

• First, contact your health-care professional to discuss alternate treatment options.
• Second, DO NOT STOP taking Pergolide without consulting your health-care professional. Stopping pergolide too quickly can be dangerous and several other effective treatments are available.

If you are a health-care professional who prescribes pergolide, you should consider the three following items:

• First, Assess your patient’s need for dopamine-agonist therapy. If continued treatment with a dopamine-agonist is necessary, another dopamine-agonist should be substituted for pergolide. There are other dopamine agonists approved for the treatment of Parkinson’s disease that are not associated with heart valve damage. Published transition regimens describe the conversion from one dopamine-agonist to another.
• Second, if treatment with a dopamine-agonist is to be discontinued, pergolide should not be stopped abruptly, because rapid discontinuation of all dopamine-agonist therapies can be dangerous. Instead, gradually decrease the dose of pergolide.
• Third, you should tell patients who will be taken off pergolide that other effective options for treatment exist, including three other dopamine agonists that are not associated with damage to heart valves.

In 2006, a boxed warning regarding the risk of serious heart valve damage was added to the labeling for pergolide. The two recent studies, published in The New England Journal of Medicine in January 2007, confirm earlier studies that also described this problem.

Pergolide is marketed by Valeant under the trade name Permax and sold and manufactured as the generic drug pergolide by Par and Teva.

In light of this additional safety information and the availability of alternative treatments for Parkinson’s disease that do not have comparable safety problems, the companies that manufacture and sell pergolide have stopped shipping pergolide for distribution.

The companies will, in cooperation with us, work to remove from the market both Permax and generic versions of pergolide.

The effect of this voluntary withdrawal on supplies of pergolide currently in pharmacies will not be immediate. This delay will allow time for health-care professionals and patients to discuss appropriate treatment options and to change treatments.

One of the drugs that was included in the recent studies showing increased chance of heart valve problems is another dopamine agonist — Dostinex — also known by the generic name Cabergoline.

This drug is approved in the united states for the treatment of hyperprolactinemic [hyper-pro-lack-teh-knee-mick] disorders — conditions in which there are elevated levels of prolactin [pro-lack-tin] in the blood.

Dostinex is not approved in the United States for the treatment of Parkinson’s disease. For hyperprolactinemic disorders, a considerably lower dose of Dostinex is used. At these lower doses of Dostinex, there appears to be little chance of heart problems; therefore, Dostinex will remain on the U.S. market for the treatment of hyperprolactinemic disorders.

We are working with the manufacturers of pergolide to determine if it is possible to make the drug available to those few patients who are currently taking pergolide under these two conditions:

• First, where previous efforts to switch to a different treatment have been unsuccessful.
• Or, second, where efforts subsequent to this advisory to switch therapies are also unsuccessful.

In the interim, health-care professionals and patients should consider all treatment options with the understanding that in the future, the drug may no longer be available.

We are asking health-care professionals to report serious adverse events in connection with pergolide to us through the MedWatch program by phone at 1-800-F-D-A-ten-88 or by the Internet at F-D-A dot gov slash MedWatch.

Updated information about drugs with emerging safety concerns is available 24 hours a day at our Web site W-W-W dot F-D-A dot gov slash C-D-E-R.

[music]

Do I Have a Permax or Pergolide Lawsuit?

If you or a loved one have taken Permax or Pergolide and suffered from any of the side effects listed below, you should contact us immediately. You may be entitled to compensation and we can help.

Side Effects

• heart-valve damage (Aortic and Mitral Valve Injuries)
• Primary Pulmonary Hypertension
• cardiac valvulopathy
• valvular heart disease
• leaky heart valves
• pulmonary fibrosis (retroperitoneal, pleural, and pericardial fibrosis)

Click Here To Learn More: Permax (Pergolide) Recall Information

Source | FDA

Agency Working with Product Manufacturers

The U.S. Food and Drug Administration (FDA) today announced that manufacturers of pergolide drug products, which are used to treat Parkinson’s disease, will voluntarily remove these drugs from the market because of the risk of serious damage to patients’ heart valves.

The products being withdrawn are Permax, the trade name for pergolide marketed by Valeant Pharmaceuticals, and two generic versions of pergolide manufactured by Par and Teva. Pergolide is in a class of medications called dopamine agonists and is used with levodopa and carbidopa to manage the symptoms (tremors and slowness of movement) of Parkinson’s disease.

In 2006, an estimated 12,000 patients received prescriptions for pergolide from retail pharmacies in the United States. Patients taking pergolide should contact their doctors to discuss alternate treatments. Patients should not stop taking the medication, as stopping pergolide abruptly can be dangerous.

There are alternative therapies available for Parkinson’s disease, including three other dopamine agonists that have not been associated with valvular heart disease. The removal of pergolide products is not expected to adversely affect patient care because of the alternative therapies available.

“Based on important new drug safety information, FDA has been working with the manufacturers of pergolide products to voluntarily remove these drugs from the market,” said Douglas Throckmorton, M.D., deputy director of FDA’s Center for Drug Evaluation and Research. “The FDA’s increased evaluation of post-market safety is benefiting the public because, in this case, as new data about the product became available, we were able to remove a less safe drug from the market.”

Two recent New England Journal of Medicine studies confirm previous findings associating pergolide with increased chance of regurgitation (backflow of blood) of the mitral, tricuspid, and aortic valves of the heart. Valve regurgitation is a condition in which valves don’t close tightly, allowing blood to flow backward across the valve. Symptoms include shortness of breath, fatigue and heart palpitations.

In light of this additional post-market safety information, the companies that manufacture and sell pergolide will stop shipping pergolide for distribution and, in cooperation with FDA, will withdraw the products from the market.

Permax was approved in 1988 for Eli Lilly and Company as an adjunctive therapy with levodopa in Parkinson’s disease. Valvular heart disease was first described in association with pergolide in 2002. In 2003, FDA asked Lilly to add valvulopathy (abnormality of cardiac valves) to the warnings section of Permax labeling, at which time a Dear Healthcare Practitioner letter was sent by Lilly. In 2006, the warning was upgraded to a black box warning, the FDA’s strongest form of warning, because of new data concerning risks of heart valve damage.

FDA today is issuing a Public Health Advisory (PHA) detailing the removal of pergolide products from the market. The PHA, which is available at www.fda.gov/cder/drug/advisory/pergolide.htm includes information and recommended actions for physicians, pharmacists and patients.

The effect of the voluntary withdrawal on supplies of pergolide currently in pharmacies will not be immediate. This delay will allow time for health care providers and patients to discuss appropriate treatment options and time to change treatments.

FDA is working with the manufacturers of pergolide to determine if it might be possible, once the drug is withdrawn from the market, to make the drug available under an Investigational New Drug Application (IND) for those few patients who are currently receiving pergolide and who cannot be successfully converted to other available treatments.

###

Source | The New York Times

By DENISE GRADY

Two drugs used to treat Parkinson’s disease and other disorders can seriously damage heart valves, researchers are reporting.

The drugs are pergolide, sold as Permax, and cabergoline, sold as Dostinex. Permax is approved in the United States and overseas for Parkinson’s. Dostinex is used for Parkinson’s in other countries but is approved in this country only for a hormonal disorder, hyperprolactinemia.

New findings on the drugs are described in two studies being published today in The New England Journal of Medicine.

Permax already carries a black-box warning label — the strongest warning required by the Food and Drug Administration — about an increased risk of heart-valve problems. Such warnings, bordered in black, appear at the top of prescribing information to get doctors’ attention. The Permax warning was added in 2003, based on a small number of reported cases. It includes this statement: ‘’Some patients have required valve replacement, and deaths have been reported.'’

A milder warning about valve problems was added to Dostinex just last month. It is identified as a ‘’precaution,'’ which means there is no black box, and the advice is in a less obvious part of the prescribing information for doctors.

A spokeswoman for the drug agency said that it had worked with the makers of both drugs on the labeling changes, but that she did not know whether the new findings would lead to further changes.

Dr. Michael S. Okun, the medical director for the National Parkinson Foundation, said people taking Permax or Dostinex for Parkinson’s should be told about the new information and given a chance to switch to other drugs. He added that patients who were just starting treatment should be given other drugs. Safer, equally effective drugs are available, he said.

Dr. Okun, who was not involved in the two studies, is also co-director of the Parkinson Disease and movement disorders center at the University of Florida in Gainesville.

He said doctors in poorer countries might favor Permax and Dostinex because they are cheaper than some other Parkinson’s drugs. But Dr. Okun said it would cost no more to switch patients to the old Parkinson’s standby drug, L-dopa or levodopa, which has side effects of its own, but has never been known to damage heart valves.

‘’Patients should be given the choice of what to do,'’ Dr. Okun said. ‘’There are lots of people worldwide who have used these drugs successfully. Some patients, after being educated, may decide they want to accept the potential risk. Others may want to switch.'’

Another researcher took a far different view.

‘’I would just recommend not prescribing these drugs,'’ said that researcher, Dr. Bryan L. Roth, who wrote an analysis of the research that accompanied the articles in The Journal. Dr. Roth is a professor of pharmacology and medicinal chemistry at the University of North Carolina School of Medicine and director of the psychoactive drug screening program at the National Institute of Mental Health.

Dr. Roth called the risk of valve disease ‘’extraordinarily high'’ and asked: ‘’Why would you want to subject your patient to this kind of risk? I wouldn’t.'’

Valeant Pharmaceuticals, which makes Permax, issued a statement by e-mail calling the drug safe and effective for Parkinson’s. But Valeant added that it no longer promoted the drug, which was originally made by Eli Lilly.

Dr. Michael Berelowitz, senior vice president of Pfizer, which makes Dostinex, said the company had received fewer than 100 reports of valve problems from the drug, mostly in people with Parkinson’s.

The two new reports involve only Parkinson’s. The results should not be applied to patients who take Dostinex for the hormone disorder because they take far smaller doses of the drug than do patients with Parkinson’s, said Dr. David L. Kleinberg, a professor of medicine and director of the neuroendocrine unit at New York University’s medical school.

The hormone disorder affects tens of thousands of people in the United States, mostly women, said Dr. Shlomo Melmed, an endocrinologist and a senior vice president of Cedars-Sinai Medical Center in Los Angeles. Men can develop the disorder, and some need higher doses of Dostinex than do women, Dr. Melmed said, so those men should be monitored for heart valve problems.

Correction: January 19, 2007, Friday An article on Jan. 4 about heart-valve problems linked to two drugs for Parkinson’s disease misstated the year that one of them, Permax, added a black-box warning label, the strongest warning required by the Food and Drug Administration. It was 2006, not 2003.

Neither drug is a big seller. About 73,000 prescriptions were written for Permax last year, representing $10.5 million in the billion-dollar market for Parkinson’s drugs in the United States, according to IMS Health, which tracks drug sales.

About 1.5 million Americans have Parkinson’s, according to the National Parkinson Foundation. Dostinex sales in the United States totaled about $88 million in 2005, and about 87,000 prescriptions were written, according to Wolters Kluwer Health, an information company in the Netherlands.

The two new studies are larger than previous ones, and they confirm the higher risk of valve damage in people taking either drug for Parkinson’s. The studies also find that the valve problem is more common than initially thought, and that people who took the highest doses for the longest time had the greatest risk.

One study, from the Istituti Clinici di Perfezionamento in Milan, included 155 patients with Parkinson’s and found that 23 percent of those taking Permax and 29 percent of those taking Dostinex had damaged heart valves, compared with only almost 6 percent of control subjects not taking the drugs.

The other study, based on the records of more than 11,000 patients with Parkinson’s in Britain, found that valve problems were seven times as likely in people taking Permax as in control subjects and five times as likely in those taking Dostinex.

Dr. Roth said the drugs produced the same kind of valve damage caused by the weight loss combination fen-phen, which led to the withdrawal of two drugs, Pondimin and Redux, in 1997. The drugs cause cells to multiply in the heart valves, which causes the valves to thicken so much that they can no longer open and close normally.

Correction: January 19, 2007, Friday An article on Jan. 4 about heart-valve problems linked to two drugs for Parkinson’s disease misstated the year that one of them, Permax, added a black-box warning label, the strongest warning required by the Food and Drug Administration. It was 2006, not 2003.

Correction: January 19, 2007, Friday An article on Jan. 4 about heart-valve problems linked to two drugs for Parkinson’s disease misstated the year that one of them, Permax, added a black-box warning label, the strongest warning required by the Food and Drug Administration. It was 2006, not 2003.

Do I Have a Permax or Dostinex Lawsuit?

If you or a loved one have taken Permax or Dostinex and suffered from any of the side effects listed below, you should contact us immediately. You may be entitled to compensation and we can help.

Source | Associated Press

By MARILYNN MARCHIONE

The risk of heart valve damage with two drugs for Parkinson’s disease may be far greater than was known, new research suggests. The drugs are not the main treatment for Parkinson’s, but one is also sometimes used to treat restless legs syndrome.

A study by Italian researchers found that roughly one-fourth of Parkinson’s patients taking pergolide or cabergoline, sold as Permax, Dostinex and other brands, had moderate to severe heart valve problems. Another study, by German doctors, found that users of either drug were five to seven times more likely to have leaky heart valves than those on other types of Parkinson’s medications. Both studies were reported in Thursday’s New England Journal of Medicine.

“This is an extraordinarily high risk,” said Dr. Bryan Roth, a pharmacology professor at the University of North Carolina at Chapel Hill.

“It’s a bad side effect. As far as I know, there are no medications that can reverse it,” and valve replacement surgery is the only solution, he said.

Roth had no role in the studies but directs a drug screening program for the National Institute of Mental Health. He also published a paper several years ago warning that these drugs appeared to trigger the same heart-related mechanism that the fen-phen diet combination did. The diet pills, sold as Pondimin and Redux, were pulled from the market in 1997 after they were linked to valve problems.

One of the Parkinson’s drugs _ pergolide, sold as Permax and other brands _ also is used to treat restless legs syndrome. Cabergoline, sold as Dostinex, Cabaser and other names, is mostly used in Europe.

About half a million people had taken Permax during its first 14 years on the market when its developer, Eli Lilly and Co., added valve damage to the potential side effects listed on the package insert in 2003. But the company said the risk was extremely low _ five in 100,000 users.

Roth believed there were more cases, a theory he said the new studies confirmed.

“This is an example of, if you don’t look for it, you don’t see it,” said Dr. C. Warren Olanow, chairman of neurology at Mount Sinai School of Medicine in New York, who had no role in the work. The findings will lead more doctors to prescribe other Parkinson’s treatments, he said.

About 1.5 million Americans and 6 million people worldwide have Parkinson’s disease, which results in tremors, loss of muscle control and sometimes death.

It’s caused by a lack of the brain chemical, dopamine. The main treatment is levodopa, which spurs the body to make more dopamine. Pergolide and cabergoline often are given in addition to that drug or in place of it, especially if symptoms worsen over time.

In one study, Dr. Renzo Zanettini and others at the Instituti Clinici di Perfezionamento in Milan obtained echocardiogram images of the hearts of 155 patients taking various Parkinson’s medications and a comparison group of 90 healthy people.

Moderate to severe valve problems were seen in 23 percent of those on pergolide and nearly 29 percent of those on cabergoline but none of those on other Parkinson’s drugs and less than 6 percent of the comparison group. The study was paid for by the Milan clinic and two Parkinson’s foundations.

In the other study, Dr. Rene Schade and colleagues in Berlin and in Montreal used records from more than 11,400 Parkinson’s patients in the United Kingdom. The rate of newly diagnosed leaky valves was increased among pergolide and cabergoline users but not the others, they found. The Canadian government and a drug company provided partial support for the study. Many researchers in both studies have consulted for Parkinson drug makers.

Pergolide sales have dropped in recent years but still amounted to more than $10 million last year in the United States, according to IMS Health, a health care information firm.

The rights to Permax in the U.S. now belong to Valeant Pharmaceuticals of Aliso Viejo, Calif. A company statement said Permax is safe and effective, but Valeant is no longer promoting the product. All such drugs should be used “with caution,” the statement says.

Cabergoline is approved in the U.S. for treating a hormone problem, excessive prolactin in the blood, but not Parkinson’s.

Roth has been urging companies developing new drugs to test for the mechanism involved in the Parkinson and fen-phen pills, saying those that that have it shouldn’t be sold.

Do I Have a Permax or Dostinex Lawsuit?

If you or a loved one have taken Permax or Dostinex and suffered from any of the side effects listed below, you should contact us immediately. You may be entitled to compensation and we can help.

Source | The New England Journal of Medicine

Two “dopamine agonist” drugs commonly used to treat Parkinson’s disease — pergolide (Permax; Eli Lily) and cabergoline (Dostinex; Pfizer) — may raise the risk of heart valve regurgitation, according to the findings of two European studies appearing in The New England Journal of Medicine this week.

The new findings support what has been seen in earlier studies.

In the first study, Dr. Rene Schade, from Charite-Universitatsmedizin Berlin, and colleagues assessed dopamine agonist use among 31 patients who were prescribed a drug for Parkinson’s disease and were later diagnosed with cardiac valve regurgitation, in which the valve fails to seal properly in the reverse-flow direction. Each case patient was matched to up to 25 “control” subjects by age and sex.

The case patients included six taking Permax, six on Dostinex and 19 who had not taken any dopamine agonist in the last year.

The investigators found that current use of Permax or Dostinex raised the risk of valve regurgitation by 7.1- and 4.9-fold, respectively. Taking other dopamine agonists seemed to have no effect on the risk of cardiac valve regurgitation.

In the second study, Dr. Renzo Zanettini, from the Istituti Clinici di Perfezionamento in Milan, and colleagues assessed valve regurgitation in 64 Permax users, 49 Dostinex users, 42 users of other dopamine agonists, and 90 control subjects.

Regurgitation was noted in roughly 23 percent of Permax users, 29 percent of Dostinex users, none of the users of other dopamine agonists, and 6 percent of controls. The severity of regurgitation with Permax and Dostinex seemed to increase with the dosage of the drugs.

In a related commentary, Dr. Bryan L. Roth, from the University of North Carolina at Chapel Hill, notes that in addition to stimulating dopamine receptors, both Permax and Dostinex stimulate serotonin receptors, a key step in the progression of drug-induced valve disease.

Roth advises doctors to avoid prescribing drugs that are potent serotonin receptor agonists such as Permax and Dostinex.

Do I Have a Permax or Dostinex Lawsuit?

If you or a loved one have taken Permax or Dostinex and suffered from any of the side effects listed below, you should contact us immediately. You may be entitled to compensation and we can help.

Source | FDA 

Eli Lilly and Company
Lilly Corporate Center
Indianapolis, Indiana 46285
Dear Health Care Professional,

During postmarketing surveillance for Permax®, a small number of individuals have been identified as developing cardiac valvulopathy involving one or more valves during Permax therapy. Based on Lilly safety data and scientific publications, the pathological assessment of valves that were surgically removed was consistent with the valvulopathy associated with carcinoid syndrome and with the use of other ergot alkaloid drugs. While a clear causal relationship between pergolide and the valvulopathy seen in these patients can not be established, given the nature of the lesions and known similar effects of other ergots, the Warnings section of the US Package Insert for Permax will be modified to reflect these reports.

In the reports made to Lilly, aortic, mitral and tricuspid valves were involved. In some cases the symptoms or manifestations of valvulopathy improved with cessation of pergolide therapy. Valve replacement was required in two patients.

It is not known whether the fibrotic valvular changes are related to retroperitoneal, pleural, and pericardial fibrosis, which are very rare but well known adverse effects seen with Permax.

Since Permax was first launched in the United States in 1989, a very limited number of cases have been reported to Lilly and to the FDA. Of the estimated 500,000 people who have been treated with pergolide since 1989, valvulopathy has been reported in less than 0.005%.

Based on these reports, the Warnings section of the US Package Insert for Permax will be modified as follows (new wording underlined):

Serous Inflammation and Fibrosis–There have been rare reports of pleuritis, pleural effusion, pleural fibrosis, pericarditis, pericardial effusion, cardiac valvulopathy involving one or more valves, or retroperitoneal fibrosis in patients taking pergolide. In some cases, symptoms or manifestations of cardiac valvulopathy improved after discontinuation of pergolide. Pergolide should be used with caution in patients with a history of these conditions, particularly those patients who experienced the events while taking ergot derivatives. Patients with a history of such events should be carefully monitored clinically and with appropriate radiographic and laboratory studies while taking pergolide.

If you have additional questions regarding Permax, you may contact Amarin Pharmaceuticals, Inc., our US licensee for Permax, at 1-800-969-4877.

Sincerely,

Valerie E. Simmons, MD, FFPM
Director
Worldwide Pharmacovigilance and Epidemiology
Eli Lilly and Company

Permax® is indicated as adjunctive treatment to levodopa/carbidopa in the management of the signs and symptoms of Parkinson’s disease. Please see accompanying Prescribing Information. Permax is a registered trademark of Eli Lilly and Company, and is licensed exclusively in the United States to Amarin Pharmaceuticals, Inc.