United States of America - During post-marketing surveillance of pergolide mesilate (Permax®), a small number of individuals have been identified as developing cardiac valvulopathy involving one or more valves. Pergolide is indicated as adjunctive treatment to levodopa/carbidopa in the management of symptoms of Parkinson disease. Of the estimated 500 000 people who have been treated with pergolide since 1989, valvulopathy has been reported in less than 0.005%.

The pathological assessment of valves that were surgically removed was consistent with valvulopathy associated with carcinoid syndrome and with the use of other ergot alkaloid drugs. In the reports made to the manufacturer, 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, or pericardial fibrosis, which are very rare but recognized adverse effects seen with pergolide mesilate.

The Warnings section of the US Package Insert has been modified as follows:

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 experience the events while taking ergot derivatives. Patients with a history of such events should be carefully monitored and with appropriate radiographic and laboratory studies.

Reference: FDA Talk Paper, T03-06, 23 January 2003. http://fda.gov/medwatch/safety/2003 permax.htm