Big problem with Cabergoline
By Gene Emery and Toni Clarke Thu Jan 4, 8:21 AM ET
BOSTON (Reuters) - Two Parkinson’s disease drugs cause the same kind of heart damage that led to the withdrawal of the diet drug combination “fen-phen,” according to two studies published on Wednesday.
Patients taking the drugs pergolide, developed by Eli Lilly & Co. and sold under the brand name Permax, and cabergoline, developed by Pfizer Inc. and sold under the brand Dostinex, had a sharply higher risk of heart valve damage than those taking other therapies, the studies said.
The studies, one of which analyzed the records of 11,417 patients in Britain and one of which tested 245 patients in Italy, reinforce the results of earlier, smaller studies showing drugs that activate a cellular receptor known as 5-HT2b can cause damage to the heart valve, a serious condition that can lead to heart failure and sudden death.
“We recommend that physicians not prescribe drugs that have this biochemical property,” said Bryan Roth, a researcher at the University of North Carolina, Chapel Hill, who was not involved in the trials, but viewed the data and commented on it in The
New England Journal of Medicine, where both studies appeared.
Michael Berelowitz, a Pfizer senior vice president, said cabergoline has very modest sales and is only approved in the United States for hyperprolactinemia — a condition in which excessive amounts of the hormone prolactin enter the bloodstream due to benign tumors of the pituitary gland.
He said benefits of the Pfizer drug, which is sold in Europe for Parkinson’s disease, as well as hyperprolactinemia, outweigh the increased risk of heart valve damage, which is noted in the drug’s package insert label.
Lilly officials could not immediately be reached for comment.
Such drugs also include the migraine headache drug ergotamine and the amphetamine derivative known as “ecstasy.”
Roth said his team, in a separate piece of research that has yet to be published or reviewed by the scientific community, has identified several other big-selling drugs that have until now not been known to activate the 5-HT2b receptor.
He declined to reveal the names of the drugs until the research has been published.
“We recommend that every drug be screened at this receptor before it goes into humans,” Roth told Reuters in an interview. “It costs just pennies per drug for such a screen.”
The British study showed patients taking pergolide were 7.1 times more likely to develop heart valve damage than those who took other treatments. Patients taking the highest doses of the drug had a 37 times greater risk.
The study showed patients taking cabergoline were 4.9 times more likely to develop heart valve damage. At higher doses patients were 50.3 times more likely to suffer damage.
Both drugs are available in generic form.
A second study, conducted in Italy, tested 245 people, of whom 155 had Parkinson’s disease. Of the diseased population, one group received pergolide, one group received cabergoline and one group received an alternative Parkinson’s treatment. The non-diseased control group received nothing.
The results showed that 23.4 percent of patients taking pergolide and 28.6 percent of patients taking cabergoline suffered heart damage, compared with just 5.6 percent in the control group.
“These are huge risks,” said Roth.
He added they were similar to the kind of damage seen with fen-phen, whose main ingredients were withdrawn in 1997 and forced the drug-maker Wyeth to take more than $21 billion in charges to cover liabilities.
Wyeth’s recalled drugs were fenfluramine, or Pondimin, and dexfenfluramine, or Redux. To make fen-phen, one or the other was combined with another drug called phentermine that is still sold by other companies.
Wyeth, then called American Home Products, recalled Pondimin and Redux after some of the 6 million Americans who had taken fen-phen developed heart-valve problems.
Roth said pergolide is also used to treat restless leg syndrome, a condition in which patients feel a crawling sensation in their legs combined with a need to move them.
(Additional reporting by Ransdell Pierson in New York)