The MHRA has issued the following statement in response to the announcement by the Food and Drug Administration in relation to the withdrawal of pergolide.
› FDA press release: FDA Announces Voluntary Withdrawal of Pergolide Products (external link)
The Food and Drug Administration in the USA is working with manufacturers to voluntarily withdraw pergolide from the market in the USA because of the risk of damage to heart valves associated with pergolide. The effect of this withdrawal will not be immediate to allow time for patients and prescribers in the USA to discuss appropriate alternative treatment.
The MHRA has monitored the issue of heart valve damage with pergolide (brand name Celance) for a number of years. Warnings were issued about this issue through the drug safety bulletin ‘Current Problems in Pharmacovigilance’ in 2003. In late 2004 / early 2005 the use of pergolide was restricted to use under specialist supervision in patients who had failed therapy with other (non-ergot) medicines for Parkinson’s disease. In addition, monitoring requirements for regular echocardiograms were added in the EU to minimise risk to patients. The manufacturer for pergolide initiated a survey to monitor the effectiveness of the risk minimisation measures and a study to clarify the frequency of heart valve damage in users of pergolide. The safety of pergolide is kept under review by the MHRA and the European Pharmacovigilance Working Party.
The restrictions and monitoring requirements put in place in the UK in early 2005 were implemented to allow access to pergolide for patients who responded well to the product while monitoring the patient carefully to identify any signs of adverse effects. The usage of pergolide in the EU has fallen considerably since the measures were implemented. Over the last five years the estimated number of patients taking pergolide has fallen by approximately two-thirds.
The safety of pergolide and the effectiveness of the risk minimisation measures implemented in the EU in 2004/5 have been continually monitored. There will be further review of this issue at the European Pharmacovigilance Working Party in April to consider what further action is required in the EU to minimise risk.
Recent publications (1, 2) have reported a similar frequency of heart valve damage with cabergoline (Cabaser) as with pergolide and as a result, the same restrictions are being applied to the use of cabergoline for Parikinson's disease as for pergolide. These are:
- Restriction of the indication for use of cabergoline in the management of the signs and symptoms of Parkinson’s disease (PD) to second line therapy in patients who are intolerant to or fail treatment with a non-ergot compound, as monotherapy, or as adjunctive treatment to levodopa plus dopa-carboxylase inhibitor;
- Contraindication in patients with a history of fibrotic disorders (e.g. fibrosis of the lungs) and/or anatomical evidence of heart valve damage;
- Warnings regarding fibrosis and heart valve damage, as well as patient monitoring requirements.
A letter is being sent to health professionals in the UK to inform them of these restrictions. Any patient who is concerned should not stop their medicine but should discuss their treatment with their doctor.
1 Schade R et al. Dopamine Agonists and the Risk of Cardiac-Valve Regurgitation, N Engl J Med 2007; 356-29
2 Zanettini R et al. Valvular Heart Disease and the Use of Dopamine Agonists for Parkinson’s Disease, N Engl J Med 2007; 356-39
