Pergolide and or Cabergoline

FDA Public Health Advisory Date created: March 29, 2007

Pergolide (marketed as Permax)and Cabergoline (marketd as Dostinex) are withdrawn because they cause valvular heart damage.

Used in the treatment of Parkinson's disease and Restless Legs Syndrome (RLS)

FDA Notice Of Withdrawal

The FDA is 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 And Cabergoline

The New England Journal of Medicine reported on January 4, 2007 that two drugs long prescribed to treat Parkinson's disease, restless leg syndrome and to prevent lactation in new mothers have been linked to the very same heart-valve problems as the combination of the diet drugs Fen/Phen. There are five other drugs used to treat the disease that are considered to be much safer.(See bottom of this page). Two studies published in this week's journal present strong evidence that the two drugs cause scarring of heart valves in nearly 30 percent of Parkinson's patients.

Ergot Derivatives

The drugs are PERGOLIDE AND CABERGOLINE. They are derived from a fungus called ergot which has long been known to cause heart valve problems. One of the studies was performed by a group of Italian doctors which found that out of 155 patients, 24% of patients taking PERGOLIDE and 28.6% of patients taking CABERGOLINE were found to have clinically important regurgitation (moderate to severe, grade 3 to 4).

How The Drugs Cause Heart Valve Problems Just Like Fen Phen

The drugs simulate dopamine which is needed for the brain to function properly. However, because they are ergots, they may induce fibrotic changes in the leaflets and in the mitral subvalvular apparatus, causing thickening, retraction and stiffening of valves and resulting in incomplete leaflet coaptation and valve regurgitation. The valvular abnormalities seen with ergot derived dopamine agonists are similiar to those observed in patients receving antimigraine ergot alkaloid agents (such as ergotamine and methysergide), or the anorectic drugs fenfluramine and dexfenfluramine. All the implicated drugs have been shown to be full of partial agonists of the serotonin receptor subtype 5-TH 2b, which is expressed in heart valves and is known to mediate mitogenesis (cell growth). Proliferation of fibroblasts (cells that develope into connective tissue) may therefore occur within the valve tissue when the 5-HT 2b receptor is stimulated.

Pergolide is a member of a class of drugs known as dopamine agonists and is used with levodopa and carbidopa to manage the signs and symptoms (tremors and slowness of movement) of Parkinson’s disease.

Parkinson's Patients Should Do The Following

Contact their healthcare professional to discuss alternate treatment options.
2. NOT stop taking Pergolide without consulting their healthcare professional, since stopping pergolide too quickly can be dangerous and several other effective treatments are available.

Healthcare Professionals Should Do The Following

Healthcare professionals who prescribe pergolide should consider the following:

1. Assess the patient’s need for dopamine agonist (DA) therapy. If continued treatment with a DA is necessary, another DA 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 DA to another.

2. If treatment with a DA 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.

3. Patients who will be taken off pergolide should be told that other effective options for treatment exist, including three other DAs that are not associated with damage to heart valves.

Boxed Warning In 2006:

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.

Withdrawal Of Drugs For Treatment Of Parkinson's Disease

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 and will, in cooperation with FDA, work to remove from the market both the name brand Permax (pergolide) and the 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 healthcare professionals and patients to discuss appropriate treatment options and to change treatments.

Cabergoline (Dostinex) Can Be Used To Treat Hyperporlactinemic Disorders

One of the drugs that was included in the recent studies showing increased chance of heart valve problems is Dostinex (cabergoline), another dopamine agonist. This drug is approved in the U.S. for the treatment of hyperprolactinemic disorders (conditions in which there are elevated levels of prolactin in the blood). Dostinex is not approved in the U.S. 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 US market for the treatment of hyperprolactinemic disorders.

FDA Exceptions

The FDA is 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 where previous efforts to switch to a different treatment have been unsuccessful, or where efforts subsequent to this advisory to switch therapies are also unsuccessful. In the interim, healthcare professionals and patients should consider all treatment options with the understanding that in the future, the drug may no longer be available.

What To Do Next?

Talk to your doctor and ask about getting an echocardiogram test to determine if you have any heart valve damage. Also inquire about being prescribed one of the other five non-ergot drugs appropriate for the treatment of Parkinson's, restless legs syndrome and lactation arrest which are not expected to induce valvular heart disease:

Drugs That Are Considered OK At This Time

Apomorphine
Pramipexole
Bromocriptine
Lisuride
Roxindole

Read The Information On Fen Phen Diet Drugs for more information on the mechanism of heart valve problems.

Get Help

Were you injured by a defective drug or supplement? If so, please save the product and instructions for the product. Also, if you have the box the product came in that would be helpful. All of this information may be vital to proving your case. Contact us for a free evaluation of your claim. 1-866-250-1786, local 651-641-1500.

Disclaimer: Always seek the advice of a qualified legal professional regarding any legal issues you may have. You should not disregard professional advice or refrain from seeking professional advice because of anything contained in this Web site. The information contained herein is general and educational in nature and may not be current or updated. Because each case is different and each legal analysis is customized for individual clients, the information contained in this Web site should never be used to determine your legal rights.

Back to Pharmaceutical Injuries