Cardiac valvulopathy has been reported to be rare (between >1/10,000 and <1/1000) in association with the use of pergolide (Celance®, Eli Lilly) based on post-marketing surveillance database. In Singapore, the ergot-derived dopamine agonist is indicated as an adjunctive treatment to levodopa, in the management of signs and symptoms of Parkinson's disease and has been available since 1992. The potentially serious ADR prompted many regulatory agencies, including HSA, to list this adverse effect in the package insert of the drug last year.

Recently, this ADR was highlighted once again by Health Canada in response to 2 case-referent (non-prospective, non-randomised) studies1,2 where a significant number of patients treated with pergolide showed evidence of cardiac valvulopathy, suggesting that the condition may occur more frequently than what earlier postmarket reports suggested. However, as there are a number of limitations with the studies, the actual rate of cardiac valvular disease with pergolide cannot be determined at this time.

In its healthcare professional advisory, Health Canada advised physicians to assess/reassess for all patients the potential harms and benefits of ergot-derived dopamine agonists, including pergolide, against those of non ergot-derived dopamine agonists. Pergolide is not recommended in patients with a history of serious inflammation, fibrosis or cardiac valvulopathy, particularly in patients who experienced the events while taking other ergot derivatives.

It also advised that patients should undergo a cardiovascular evaluation (including an echocardiogram) to assess potential presence of an occult valvular disease before initiating treatment, and periodic clinical diagnostic monitoring (e.g. physical examination, X-ray, echocardiogram, CT scan) for development of valvular disease of fibrosis. The use of pergolide doses above 5 mg/day is not recommended, based on the post-market finding that the reporting rate for cardiac valvulopathy associated with pergolide may be greater with doses above the maximum recommended. However, cardiac valvulopathy has been reported in association with doses within therapeutic range.

HSA has received 3 local reports of cardiac valvular abnormalities associated with the drug. The 3 patients were Chinese men, ages between 55 and 71 years. They had been taking the drug for 1.7 to 5.2 years before they were found to have cardiac valve abnormalities such as mild mitral and tricuspid regurgitation and moderate aortic regurgitation after screening.

1. Van Camp G et. al. Treatment of Parkinson's disease with pergolide and relation to restrictive valvular heart disease. Lancet 2004; 363:1179-83.
   
   
2. Baseman D G et. al. Pergolide use in Parkinson Disease is associated with cardiac valve regurgitation. Neurology 2004; 63:301-4.