Permax: Up to 37 Times the Risk of Valvular Heart Disease

Aliso Viejo, CAIt's enough of a challenge to deal with the symptoms, and the reality of Parkinson's disease, without the thought that Permax the very drug helping to manage your Parkinson's, could instead attack your healthy heart.

But that's the risk with Permax. And given the fact 18 years have passed since the drug was introduced, a lot of people on Permax for a lot of years may now be wishing they hadn't taken it.

Developed to aid in the control and management of Parkinson's disease, Permax was approved for use in 1989 and since then has been prescribed to 500,000 patients with the neurological disorder that affects motor skills, and causes tremors. All seemed well until December 2002, when three Parkinson's patients at the renowned Mayo Clinic were seen to have severe valvular heart disease, or so-called 'leaky valve syndrome.' All three were on Permax for the treatment of Parkinson's.

An expanded study in 2004 linked Permax to triple the risk of heart valve damage in those patients taking Permax, which is the primary commercial name for pergolide, a dopamine agonist also available in two generic forms. In 2006 a boxed warning pointing to the concern over the potential for serious heart damage was added to the packaging of all pergolide products.

Two additional studies, published in the New England Journal of Medicine (NEJM) in January of this year, finally triggered the end to pergolide. With even more evidence of the potential risk for heart valve damage, the U.S. Food and Drug Administration (FDA) asked the makers of Permax - as well as those manufacturing generic versions - to voluntary pull pergolide products from the market. This included not only an end to the distribution of the product, but also the collection of existing stock.

Valeant Pharmaceuticals International, the makers of Permax, complied with the FDA request and agreed to stop wholesale distribution of the product.

The two studies outlined in the NEJM in January referred to the latest studies conducted in Britian, and Italy respectvely. The first involved 11,417 patients - the second, 245. Both studies appear to verify earlier findings that drugs with the capability for activation of the cellular receptor known as 5-HT2b, could lead to damage of the heart valve.

According to the larger, British study, Parkinson's patients on Permax were found to be 7.1 times more likely to develop heart valve damage, than those patients taking other medications to treat their Parkinson's symptoms. Shockingly, patients who were taking the highest recommended dosage were found to be at 37 times greater the risk.

Little wonder that Dr Bryan L Roth, professor of pharmacology and medicinal chemistry at the University of North Carolina School of Medicine and director of the psychoactive drug screening program at the National Institute of Mental Health, suggested that the risk of heart valve damage to those taking Permax, was "extraordinarily high." Dr. Roth authored a review, which accompanied the NEJM article, in January 2007.

Voluntary recall of Permax was announced March 29th of this year. At the time, Robert Temple, director for the office of medical policy for the FDA, suggested that anywhere from 12,000 to 25,000 patients in the U.S. are taking Permax. The medication should not be stopped abruptly, but rather gradually tapered in consultation with a physician.

Of noteworthy interest is the time lapse - two years - between the sounding of alarm bells in 2004, and the black box warning finally added to Permax and generic pergolide packaging in 2006. The FDA is currently embroiled in the Avandia debate, which broke this week after the diabetic drug was strongly suspected of having links to heart disease. While few would disagree with the logic that more definitive studies are required to determine the ultimate safety risk of taking the diabetic drug, and the appropriate response by the manufacturer and/or federal regulators, what has everyone puzzled is the time lapse - six years - since the first warning signs of possible trouble emerged. In the case of Avandia, flags began to fly red just a year after it was approved.

Early-warning signs appear to have been ignored. The Avandia debate, which has reverberated around the globe, has extended to the halls of Congress.

Likewise the Permax issue, and the apparent link between pergolide and valvular heart disease, is generating similar concern. While heels were dragged, how many Parkinson's patients were compromised needlessly?