January 2007: NEJM Reports That Studies Show Increased Risk Of Four To Seven Times At Normal Doses
(Posted by Tom Lamb at DrugInjuryWatch.com)
The January 4, 2007 issue of The New England Journal of Medicine (NEJM) contains articles about two case studies that provide some of the strongest evidence that treatment with the Parkinson's disease drugs Permax (pergolide) and Dostinex (cabergoline) can cause cardiac-valve dysfunction. Patients who take Permax or Dostinex, according to the NEJM articles, are four to seven times more likely to suffer damage to their heart valves than patients who did not take either of these medications.
While news of heart-valve damage associated with Permax and Dostinex is not new -- first getting some attention in 2002 -- the degree of increased risk of this serious side effect is resulting in calls for the use of these drugs to be discontinued for the treatment of Parkinson's disease.
A January 4, 2007 Wall Street Journal (WSJ) article by John Hechinger provides this insight on the reaction from the medical experts:
Bryan L. Roth, a University of North Carolina psychiatrist, said the fresh research marked the largest and most definitive findings of the heart risks of these drugs. Dr. Roth, who is also director of the National Institute of Mental Health's drug-screening program, said the findings should lead doctors to discontinue using the drugs and to tell patients to get echocardiograms to make sure they don't have damage.
"The incidence is kind of mind-blowing," said Dr. Roth, who wrote an article in the journal accompanying the studies. "It's so prevalent in people taking these medications, you kind of wonder why it was missed."
A January 3, 2007 Reuters article discussed how higher doses of Permax and Dostinex caused an even higher rate of heart-valve damage in patients:
The British study showed patients taking pergolide [brand name: Permax] 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 [brand name: Dostinex] were 4.9 times more likely to develop heart valve damage. At higher doses patients were 50.3 times more likely to suffer damage.
The January 4 WSJ article also gives some position statements from the drug companies responsible for these two ergot-derived dopamine antagonists, Permax (pergolide) and Dostinex (cabergoline).
As background, in 1989, Eli Lilly & Co. brought pergolide to market under the name Permax. Valeant Pharmaceuticals International now markets the drug in the U.S.
Jeffrey D. Misakian, a Valeant spokesman, called Permax "a safe and effective treatment for patients with Parkinson's disease." He said the company "no longer promotes the drug" but makes "it available for those who prescribe it." He said the company recently worked with the FDA to modify its label to advise physicians that the product "should be used with caution."....
Pfizer markets cabergoline in the U.S. under the brand name Dostinex not for Parkinson's but for a hormone condition, the excessive production of prolactin. The company markets it for Parkinson's in Europe under a variety of brand names. Michael Berelowitz, a Pfizer senior vice president, said its safety monitoring noted a problem a year ago, leading to labeling changes that mention heart-valve risk. But, he said, "It still has a place in the treatment of patients."
The type of heart-valve damage that can be caused by Permax and Dostinex is the same kind of heart damage that led to the withdrawal of the diet drug combination "fen-phen." Further, this damage to the heart valve can lead to heart failure and sudden death.