Parkinson's Disease Drug Permax Tied to Heart Disorders in Some Patients

Kahn Gauthier Swick is investigating possible legal actions against Amarin Pharmaceuticals, Inc., the manufacturer of the prescription drug Permax (pergolide mesylate), to recover for heart damage suffered by some patients taking the drug.

Permax is prescribed for patients suffering from Parkinson's disease, a neurological disorder that causes shaking, freezing, and other movement disorders. Concern over Permax has risen since the publication of an article in the that revealed three cases of heart valve disease in patients taking Permax.

Permax and Heart Valve Disease

While the evidence in the report is based only on three cases treated at the Mayo Clinic, the doctors who wrote the report say their evidence is enough to recommend that anyone with heart problems not take Permax, which has been used since 1989. 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 heart valve disease; two had to have valve replacement surgery. None of the three had a prior history of heart disease.

Valvular Heart Disease

Valvular heart disease is a condition that impairs heart function. The heart functions as a one-way pump to move blood through the lungs and the body. Within the heart, valves work to prevent the backward flow of blood in the heart. In patients with valvular heart disease, one or more of these valves fails to seal properly and allows significant amounts of blood to flow backwards, or regurgitate. Valvular regurgitation increases the workload on the heart and, in sufficiently severe cases, can require heart valve replacement surgery. Left unchecked and untreated, some types of valvular heart disease can progress to the point where the patient is at risk of death from heart failure.

Heart Valve Damage Associated With Permax

Permax shares characteristics with a number of other drugs that have been associated with valvular heart disease. These drugs, including the now-banned fen-phen combination, are all associated with a heightened stimulation of serotonin receptors, and one of the doctors who wrote the new report speculates that this mechanism could somehow cause the valve damage.

Cardiovascular System Damages

Cardiovascular System - Frequent: postural hypotension, syncope, hypertension, palpitations, vasodilatations, congestive heart failure; Infrequent: myocardial infarction, tachycardia, heart arrest, abnormal electrocardiogram, angina pectoris, thrombophlebitis, bradycardia, ventricular extrasystoles, cerebrovascular accident, ventricular tachycardia, cerebral ischemia, atrial fibrillation, varicose vein, pulmonary embolus, AV block, shock; Rare: vasculitis, pulmonary hypertension, pericarditis, migraine, heart block, cerebral hemorrhage.

2003 Safety Alert - Permax (pergolide mesylate)

This is the text of a letter from Eli Lilly and Company. Contact the company for a copy of any referenced enclosures.

Eli Lilly and Company
Lilly Corporate Center
Indianapolis, Indiana 46285

Dear Health Care Professional,

During postmarketing surveillance for Permax®, a small number of individuals have been identified as developing cardiac valvulopathy involving one or more valves during Permax therapy. Based on Lilly safety data and scientific publications, the pathological assessment of valves that were surgically removed was consistent with the valvulopathy associated with carcinoid syndrome and with the use of other ergot alkaloid drugs. While a clear causal relationship between pergolide and the valvulopathy seen in these patients can not be established, given the nature of the lesions and known similar effects of other ergots, the Warnings section of the US Package Insert for Permax will be modified to reflect these reports.

In the reports made to Lilly, aortic, mitral and tricuspid valves were involved. In some cases the symptoms or manifestations of valvulopathy improved with cessation of pergolide therapy. Valve replacement was required in two patients.

It is not known whether the fibrotic valvular changes are related to retroperitoneal, pleural, and pericardial fibrosis, which are very rare but well known adverse effects seen with Permax.

Since Permax was first launched in the United States in 1989, a very limited number of cases have been reported to Lilly and to the FDA. Of the estimated 500,000 people who have been treated with pergolide since 1989, valvulopathy has been reported in less than 0.005%.

Based on these reports, the Warnings section of the US Package Insert for Permax will be modified as follows (new wording underlined):

Serous Inflammation and Fibrosis--There have been rare reports of pleuritis, pleural effusion, pleural fibrosis, pericarditis, pericardial effusion, cardiac valvulopathy involving one or more valves, or retroperitoneal fibrosis in patients taking pergolide. In some cases, symptoms or manifestations of cardiac valvulopathy improved after discontinuation of pergolide. Pergolide should be used with caution in patients with a history of these conditions, particularly those patients who experienced the events while taking ergot derivatives. Patients with a history of such events should be carefully monitored clinically and with appropriate radiographic and laboratory studies while taking pergolide.

If you have additional questions regarding Permax, you may contact Amarin Pharmaceuticals, Inc., our US licensee for Permax, at 1-800-969-4877.

Sincerely,

Valerie E. Simmons, MD, FFPM
Director
Worldwide Pharmacovigilance and Epidemiology
Eli Lilly and Company

Permax® is indicated as adjunctive treatment to levodopa/carbidopa in the management of the signs and symptoms of Parkinson's disease. Please see accompanying Prescribing Information. Permax is a registered trademark of Eli Lilly and Company, and is licensed exclusively in the United States to Amarin Pharmaceuticals, Inc.

If you have taken Permax and suffered Heart Damage, Heart Valve Damage or have had Heart Valve Replacement surgery, contact us about a possible claim.