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Dangers of Pergolide
3 October 2007
Dopamine agonists used to treat AADC deficiency include ergot and non-ergot derived forms. Recently it has been reported that ergot forms of dopamine agonists, such as Pergolide and Bromocriptine can cause a serious fibrotic reaction. The newer forms of non-ergot dopamine agonists, Pramipexole and Ropinirole, are now more favoured in the treatment of AADC deficiency but do not necessarily share the same benefits as the ergot forms.
A trial by an AADC affected family to switch from ergot to non-ergot dopamine agonist had devastating affects. Both children lost their head control soon after switching drugs. Pergolide was re-instated and within 2 days the children recovered to their original state.
It is recommended that a Cardiologist should regularly monitor patients using Pergolide for complications.
Pergolide will continue to be manufactured as long as the appropriate Licence is granted and of course, there is a public demand for the drug. It has been approximated that in the last 5 years the use of Pergolide has fallen by two-thirds.
The AADC Research Trust is currently putting together a Pergolide Patient Information Leaflet, which can be presented to a Clinician caring for an AADC patient on Pergolide.
David Gaze has been investigating the latest information on Pergolide:
The use of Pergolide in the treatment of AADC
David C Gaze, Cardiac Research Scientist, Chemical Pathology, St George’s Hospital, London, United Kingdom.
What is Pergolide?
Pergolide is a dopamine receptor agonist and exerts direct action dopamine receptors. Pergolide like other dopamine receptor agonists is used in the treatment of Parkinson’s disease either alone or in conjunction with levodopa or carbidopa. Pergolide has the same action in the body as dopamine. It is used primarily to treat symptoms common to patients with Parkinson’s disease. These include stiffness, tremors, spasms and poor muscle control.
Cautions when using Pergolide
Caution on drug use is advised in patients with arrhythmia or underlying cardiac disease, history of confusion or hallucinations, dyskinesia, pregnancy, breast-feeding. Dosing should occur gradually and abrupt withdrawal should be avoided. The effects of Pergolide are antagonised when used with antipsychotics. Dopaminergic drug effects can be enhanced when used in conjunction with memantine. The antiparkinsonian effect is antagonised by methyldopa or metoclopramide.
What are the side effects of Pergolide?
Like all drugs Pergolide can exhibit side effects and include hallucinations, confusion, dizziness, dyskinesia, drowsiness, abdominal pain, nausea, vomiting, dyspepsia, diplopia (double vision), rhinitis, dyspnoea, pleuritis, pleural effusion, pleural fibrosis, pericarditis, pericardial effusion, cardiac valvulopathy, retroperitoneal fibrosis, insomnia, constipation or diarrhoea, hypotension syncope, tachycardia, atrial premature contractions, rash, fever. Raynaud’s phenomenon has been reported as has neuroleptic malignant syndrome.
Why is Pergolide not available in the United States of America?
In March 2007, the Food and Drug Administration (FDA) in the United States of America introduced a voluntary withdrawal of Pergolide products from the US market (1). This is due to the associated risk of damage to heart valves. Two case control studies published in the January 2007 found significantly increased rates of valvular dysfunction in patients with Parkinson's disease taking Pergolide and Cabergoline (2,3). The findings of these two studies are consistent with abundant clinical and mechanistic evidence that activators of the serotonin receptor 5-hydroxytryptamine 2B (5-HT2B), such as Pergolide and Cabergoline, cause a distinct form of fibrotic valvulopathy (valve stiffening).
Permax, the trade name for Pergolide marketed by Valeant Pharmaceuticals, and two generic versions of Pergolide manufactured by Par and Teva are no longer available in the USA.
The use of Pergolide in the United Kingdom
The Medicines and Healthcare products Regulatory Agency (MHRA) which regulates drug use in the United Kingdom have released their own statement on the use of Pergolide (4).The use of pergolide was restricted by the MHRA for use under specialist supervision in patients who had failed therapy with other medicines for Parkinson’s disease. Monitoring requirements for regular echocardiograms (ECG, heart traces) were required 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 were implemented to allow those patients who responded well to Pergolide therapy to continue with its use under careful monitoring. It has been approximated that in the last 5 years the use of Pergolide has fallen by two-thirds.
More recently, in April 2007, The Pharmacovigilance Expert Advisory Group issued a statement on the use of Pergolide and the risk of heart valve disease. In light of the two studies published and the action taken by the FDA to withdraw Pergolide, the group advised the risk and benefits for Pergolide and other dopamine agonists should be reviewed on a Europe wide basis which has been taken forward for further discussion within Europe. Further discussion by this group in May 2007 resulted in the group endorsing a procedure to review the risk and benefit of ergot-derived dopamine agonists (including Pergolide) for the treatment of Parkinson’s disease. No further reports are given by the group who met in June and July 2007.
Where can I get more information?
Medicines and Healthcare products Regulatory Agency (MHRA):
www.mhra.gov.uk
US Food and Drug Administration:
www.fda.org
Patient UK:
www.patient.co.uk/showdoc/30002976
References
1. Food and Drug Administration. FDA news. FDA Announces Voluntary Withdrawal of Pergolide Products. Agency Working with Product Manufacturers - P07-54 March 29, 2007. http://www.fda.gov/cder/drug/advisory/pergolide.htm
2. Schade R, Andersohn F, Suissa S, et al. Dopamine agonists and the risk of cardiac-valve regurgitation. N Engl J Med 2007; 356:29-38.
3. Zanettini R, Antonini A, Gatto G, et al. Valvular heart disease and the use of dopamine agonists for Parkinson's disease. N Engl J Med 2007; 356:39-46.
5. MHRA Pharmacovigilance Expert Advisory Group: Summary of the Meeting of the Pharmacovigilance Expert Advisory Group. 18th April 2007
Legal statement:
The advice given in this news brief is for information purposes only. It is not a substitute for professional medical professional advice intended for self diagnosis or endorsed any treatment. Always seek the advice of your physician or other qualified health care provider. Nothing contained in this news brief is intended to constitute a medical diagnosis or treatment and is not recommending or endorsing any specific tests, products, procedures, opinions, or other information that may be mentioned in this news brief.
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