- Two drugs once commonly used to treat Parkinson's disease,
pergolide and cabergoline, produce heart valve defects in as many as
a quarter of the patients who use them, Italian and German
researchers reported today.
Scattered findings from smaller studies have already suggested that
the drugs pose a risk, but the two new papers in the New England
Journal of Medicine show that the risk is much higher than
suspected.

"This is not a rare side effect," said Dr. Bryan L. Roth of the
University of North Carolina at Chapel Hill, who wrote an editorial
accompanying the report. "That's an extraordinarily high incidence.
That makes this a serious problem."

Many U.S. physicians have stopped prescribing pergolide in light of
the earlier reports, and cabergoline is not approved in this country
for treatment of Parkinson's, said Robin A. Elliott, executive
director of the Parkinson's Disease Foundation.

Cabergoline, however, is approved for other uses, such as treating
brain tumors, and is sometimes used off-label for the treatment of
Parkinson's.

The drugs, which are available in generic form from a variety of
producers, "have been around a long time, and a large number of
people have potentially been exposed to them," said Dr. Michael S.
Okun, medical director of the National Parkinson Foundation. And the
drugs are much more widely used in Europe and developing countries
because they cost less than newer drugs that do the same thing, he
added.

Some patients who have done well on pergolide will decide to
continue to take it, Okun said. Valeant Pharmaceuticals
International of Aliso Viejo, which markets pergolide under the
brand name Permax, said in an e-mailed statement that "Permax is a
safe and effective treatment for patients with Parkinson's disease.
Although Valeant no longer promotes the product, we still make it
available for those who prescribe it."

Similar heart valve problems led to the withdrawal of the diet drugs
fenfluramine and dexfenfluramine — part of the now notorious fen-
phen drug combo — from the market in 1997.

The drugs cause the heart valves to develop fibrous deposits that
produce leakage of blood back into the heart. That causes the heart
to overwork, which can lead to heart failure and death.

The problem is readily detected by ultrasound and can be fixed only
by replacing the valve.

Roth, who has a contract with the National Institutes of Health to
screen every drug on the U.S. market for the heart valve problem,
said he had found other drugs that present the same problem. He
would not identify them, however, pending the publication of his
initial results.

Parkinson's, which strikes as many as 100,000 Americans each year,
is characterized by severe tremors and rigidity in the limbs, and
loss of muscle control. It results from the death of brain cells
that produce the neurotransmitter dopamine, which plays a key role
in transmitting commands from the brain's muscle-control centers.

The most commonly used treatment is the drug levodopa, which is
converted to dopamine in the brain. Pergolide and cabergoline are
members of a family of drugs called dopamine agonists that bind to
dopamine receptors in the brain and produce effects similar to
dopamine.

The use of pergolide in this country was declining even before the
heart valve risk became known because of the development of newer
dopamine agonists, including pramipexole and ropinirole, said Dr.
Fernando Pagan of Georgetown University.

The new results make it more important for neurologists to steer
patients away from pergolide and toward the newer agents, he said.

In one study, Dr. Renzo Zanettini and his colleagues at the Istituti
Clinici di Perfezionamento in Milan, Italy, used echocardiography to
study 155 patients taking the two drugs and found "clinically
important" valve damage in 23.4% of those taking pergolide and 28.6%
of those taking cabergoline.

None of those taking other dopamine agonists showed the problems,
they said. Their study was funded by two Italian Parkinson's
foundations.

In the second study, Dr. Rene Schade of Charite-Universitatsmedizin
in Berlin studied patients with newly diagnosed cardiac valve
problems. They found that pergolide increased the risk sevenfold and
cabergoline fivefold, while other dopamine agonists did not raise
the risk.


Thomas H. Mau
1/4gh II/07(latimes.com)