Pergolide, a drug used to ease the tremors of Parkinson’s disease, may be responsible for serious heart damage, doctors at the Mayo Clinic report.
While the evidence in the report is based only on three cases treated at the clinic, the doctors say their evidence is enough to recommend that anyone with heart problems not take pergolide, which is sold as Permax and has been used since 1989 to treat the tremors and restless leg syndrome that Parkinson’s disease patients suffer.
“Further study is needed to see if this condition is under-recognized or, conversely, so rare that it escapes attention,” says Dr. Raul Espinosa, a cardiologist at the Mayo Clinic and one of the authors of the report. But, in the meantime, he and his colleagues write in the report that “pergolide should be discontinued if valvular disease is detected and no other cause identified.”
The drug’s makers say that it has had a safe record since coming on the market, but that they would consider adding the information when they update the labeling on the package.
In the cases that were treated at the clinic, three older women aged 61, 72, and 74 had been taking various doses of Permax daily for between three and seven years to treat their Parkinson’s disease. At the clinic they were diagnosed with serious valve disease; two had to have valve replacement surgery. None of the three had a prior history of heart disease.
The valve damage was quite exceptional, Espinosa says, the kind only explained by a very limited number of conditions, none of which the women had. So he and his colleagues looked for other causes and found that the women had all been taking pergolide for an extended amount of time.
The doctors knew that pergolide shares characteristics with a number of other drugs that have been associated with valvular heart disease. These drugs, including fen-phen, which is taken for weight loss, are all associated with a heightened stimulation of serotonin receptors, Espinosa says, which he speculates could somehow cause the valve damage.
Dr. Abraham Lieberman, the medical director of the National Parkinson Foundation in Miami, was one of the doctors who studied pergolide in the 1980s, when it was developed.
“There is evidence of pulmonary fibrosis that is associated with pergolide,” he says, “but there’s a 14-year history of people taking Permax, and why hasn’t this showed up sooner?”
“I don’t know the answer to that question,” Espinosa responds, “except that you have to have a certain element of good fortune and coincidence to even begin to speculate on something like this.”
He says that the first patient who was brought in for surgery for valve replacement sparked his and his colleagues’ interest because she “had a combination of a particularly unusual appearance of valves combined with a coating of fibrous cartilage material that overlay the valves.”
“This presentation is seen with a limited number of conditions, and the changes in the valves suggested only those conditions until we realized that the woman was on pergolide,” he says.
That finding led them back to their surgical records to see if any other people who had had valve replacement in the previous year had also been taking pergolide. They found one out of 17 patients who had been on the drug. At the same time, a third woman came to the Mayo Clinic with the same diagnosis of valve disease and with a history of taking pergolide for her Parkinson’s.
Espinosa says the fact that all the patients were women is not significant “with only three patients, it could easily be chance.”
He says that further study is needed to find out how common valvular disease is among Parkinson’s patients and the possible abnormalities that might occur with pergolide. “What is the risk of valve damage in relation to dosage and the duration of therapy?” he wonders.
“This drug has been on the market since 1989 and over a half million people have been treated. The Mayo Clinic findings are observations at this point, and what one wants to know is what other drugs the patients have been on during their lifetimes,” says Mike Coffee, president and chief operating officer for Amarin Corp. in San Francisco, which now manufactures the drug. Pergolide was developed by Eli Lilly and Co.
“The bottom line, however, is that we encourage doctors to check the package inserts, which are updated annually or as needed to reflect new reports, and this new information may very well be added,” Coffee says. “Doctors are experienced in this area, and if they believe that patients are at risk for developing side effects or potentially serious consequences, they should evaluate that when initiating treatment.”
Parkinson’s disease is a progressive neurological disorder resulting from the degeneration of neurons in a region of the brain that controls movement. The degeneration creates a shortage of the brain-signaling chemical known as dopamine, causing the movement impairments that characterize the disease. In the United States, at least 500,000 people are believed to suffer from Parkinson’s disease, and about 50,000 new cases are reported annually, according to the National Institute of Neurological Disorders and Stroke.