Abstract
Background
Domperidone is used to treat gastrointestinal symptoms in patients with Parkinson’s disease. Because of an increased risk of cardiac adverse events, the European Medicines Agency has issued recommendations restricting its use mainly in terms of age, dose, and treatment duration.
Objective
The aim of this study was to investigate current prescription practices of domperidone in Parkinson’s disease among French neurologists.
Methods
A cross-sectional study based on a questionnaire was conducted among French neurologists from Parkinson’s disease expert centers from the French NS-Park/FCRIN network, general hospitals, and private practice.
Results
Among the 253 neurologists who completed the questionnaire, 86 (34%) were physicians from expert centers and 167 (66%) were from other healthcare settings; 209 (83%) were aware of recommendations restricting domperidone use. The majority of neurologists (92%) declared prescribing domperidone regardless of the age of the patients. Sixty-one percent of neurologists prescribed domperidone beyond 7 days in newly diagnosed patients, 33% in patients with orthostatic hypotension, and 79% in patients receiving continuous apomorphine treatment. They did not follow the recommendation on posology in newly diagnosed patients (7% of neurologists), patients with orthostatic hypotension (10%), and patients receiving continuous apomorphine therapy (25%). Finally, only 58% of neurologists declared taking specific precautions before prescribing domperidone.
Conclusions
These findings show most French neurologists who responded to our questionnaire do not fully follow the restrictions on domperidone use, particularly in terms of treatment duration, and in patients receiving continuous apomorphine treatment. This may reflect the unmet need to prevent nausea in patients with Parkinson’s disease treated with dopaminergic drugs, particularly continuous apomorphine therapy.
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References
de Lau LM, Breteler MM. Epidemiology of Parkinson’s disease. Lancet Neurol. 2006;5(6):525–35.
Wanneveich M, Moisan F, Jacqmin-Gadda H, Elbaz A, Joly P. Projections of prevalence, lifetime risk, and life expectancy of Parkinson’s disease (2010–2030) in France. Move Disord. 2018;33(9):1449–55.
Marsden CD, Parkes JD, Rees JE. A year’s comparison of treatment of patients with Parkinson’s disease with levodopa combined with carbidopa versus treatment with levodopa alone. Lancet. 1973;2(7844):1459–62.
Rascol O, Brooks DJ, Brunt ER, Korczyn AD, Poewe WH, Stocchi F. Ropinirole in the treatment of early Parkinson’s disease: a 6-month interim report of a 5-year levodopa-controlled study. 056 Study Group. Move Disord. 1998;13(1):39–45.
Rinne UK, Bracco F, Chouza C, Dupont E, Gershanik O, Marti Masso JF, et al. Cabergoline in the treatment of early Parkinson’s disease: results of the first year of treatment in a double-blind comparison of cabergoline and levodopa. The PKDS009 Collaborative Study Group. Neurology. 1997;48(2):363–8.
Schapira AH, McDermott MP, Barone P, Comella CL, Albrecht S, Hsu HH, et al. Pramipexole in patients with early Parkinson’s disease (PROUD): a randomised delayed-start trial. Lancet Neurol. 2013;12(8):747–55.
Watts RL, Jankovic J, Waters C, Rajput A, Boroojerdi B, Rao J. Randomized, blind, controlled trial of transdermal rotigotine in early Parkinson disease. Neurology. 2007;68(4):272–6.
Barone JA. Domperidone: a peripherally acting dopamine2-receptor antagonist. Ann Pharmacother. 1999;33(4):429–40.
Agid Y, Pollak P, Bonnet AM, Signoret JL, Lhermitte F. Bromocriptine associated with a peripheral dopamine blocking agent in treatment of Parkinson’s disease. Lancet. 1979;1(8116):570–2.
Schoffer KL, Henderson RD, O’Maley K, O’Sullivan JD. Nonpharmacological treatment, fludrocortisone, and domperidone for orthostatic hypotension in Parkinson’s disease. Move Disord. 2007;22(11):1543–9.
Giaccone G, Bertetto O, Calciati A. Two sudden deaths during prophylactic antiemetic treatment with high doses of domperidone and methylprednisolone. Lancet. 1984;2(8415):1336–7.
Joss RA, Goldhirsch A, Brunner KW, Galeazzi RL. Sudden death in cancer patient on high-dose domperidone. Lancet. 1982;1(8279):1019.
Johannes CB, Varas-Lorenzo C, McQuay LJ, Midkiff KD, Fife D. Risk of serious ventricular arrhythmia and sudden cardiac death in a cohort of users of domperidone: a nested case-control study. Pharmacoepidemiol Drug Saf. 2010;19(9):881–8.
van Noord C, Dieleman JP, van Herpen G, Verhamme K, Sturkenboom MC. Domperidone and ventricular arrhythmia or sudden cardiac death: a population-based case–control study in the Netherlands. Drug Saf. 2010;33(11):1003–14.
European Medicines Agency’s Pharmacovigilance Risk Assessment Committee (PRAC). PRAC recommends restricting use of domperidone. EMA/129231/2014. Available from: https://www.ema.europa.eu/en/documents/referral/prac-recommends-restricting-use-domperidone_en.pdf. [Accessed 14 Nov 2019].
Mariani LL, Doulazmi M, Chaigneau V, Brefel-Courbon C, Carriere N, Danaila T, et al. Descriptive analysis of the French NS-Park registry: towards a nation-wide Parkinson’s disease cohort? Parkinsonism Relat Disord. 2019;64:226–34.
Ha AD, Brown CH, York MK, Jankovic J. The prevalence of symptomatic orthostatic hypotension in patients with Parkinson’s disease and atypical parkinsonism. Parkinsonism Relat Disord. 2011;17(8):625–8.
Senard JM, Rai S, Lapeyre-Mestre M, Brefel C, Rascol O, Rascol A, et al. Prevalence of orthostatic hypotension in Parkinson’s disease. J Neurol Neurosurg Psychiatry. 1997;63(5):584–9.
Velseboer DC, de Haan RJ, Wieling W, Goldstein DS, de Bie RM. Prevalence of orthostatic hypotension in Parkinson’s disease: a systematic review and meta-analysis. Parkinsonism Relat Disord. 2011;17(10):724–9.
National Institute for Health and Care Excellence (NICE). Parkinson’s disease in adults: diagnosis and management, full guideline. NICE guideline NG71, methods, evidence and recommendations. 2017 July.
Pietz K, Hagell P, Odin P. Subcutaneous apomorphine in late stage Parkinson’s disease: a long term follow up. J Neurol Neurosurg Psychiatry. 1998;65(5):709–16.
Katzenschlager R, Poewe W, Rascol O, Trenkwalder C, Deuschl G, Chaudhuri KR, et al. Apomorphine subcutaneous infusion in patients with Parkinson’s disease with persistent motor fluctuations (TOLEDO): a multicentre, double-blind, randomised, placebo-controlled trial. Lancet Neurol. 2018;17(9):749–59.
Simeonova M, de Vries F, Pouwels S, Driessen JHM, Leufkens HGM, Cadarette SM, et al. Increased risk of all-cause mortality associated with domperidone use in Parkinson’s patients: a population-based cohort study in the UK. Br J Clin Pharmacol. 2018;84(11):2551–61.
Hauser RA, Isaacson S, Clinch T. Randomized, placebo-controlled trial of trimethobenzamide to control nausea and vomiting during initiation and continued treatment with subcutaneous apomorphine injection. Parkinsonism Relat Disord. 2014;20(11):1171–6.
Acknowledgments
The authors thank the neurologists for their participation in this research and the following network and associations for their contribution to the study: the NS-Park/FCRIN network (Electronic Supplementary Material), the French Society of Neurology, and the Association des Neurologues Libéraux de Langue Française, and the Centre de Pharmacoépidémiologie (Cephepi) of the Assistance Publique – Hôpitaux de Paris for its role in the implementation and monitoring of this study.
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Funding
This study was funded by the ANSM (Agence National de Sécurité du Médicament). The “DUMP” is registered under reference EUPAS26319 and received an ENCePP Seal that recognizes studies following the ENCePP principles of standards, transparency, and independence.
Conflict of interest
The authors declare no financial relationships with any organizations that might have an interest in the submitted work in the previous 3 years; no other relationships or activities that could appear to have influenced the submitted work. Competing financial interests unrelated to the present work: Louise-Laure Mariani received research support grants from INSERM, JNLF, and The L’Oreal Foundation; received speech honoraria from CSL, Sanofi-Genzyme, Lundbeck, and Teva; was a consultant for Alzprotect, Bionure, and Digitsole; and received travel funding from the Movement Disorders Society, ANAINF, Merck, Merz, Medtronic, Teva, and AbbVie, outside the submitted work. Olivier Rascol served as a member of advisory boards for AbbVie, Adamas, Acorda, Addex, AlzProtect, Apopharma, Astrazeneca, Bial, Biogen, Britannia, Buckwang, Clevexel, INC Reasearch, Lundbeck, Lupin, Merck, MundiPharma, Neuratris, Neuroderm, Novartis, ONO Pharma, Orion Pharma, Osmotica, Oxford Biomedica, Parexel, Pfizer, Prexton Therapeutics, Quintiles, Sanofi, Servier, Sunovion, Théranexus, Takeda, Teva, UCB, Watermark, Research, XenoPort, XO, and Zambon and received a grant from Agence Nationale de la Recherche (ANR), CHU de Toulouse, France-Parkinson, INSERM-DHOS Recherche Clinique Translationnelle, MJFox Foundation, Programme Hospitalier de Recherche Clinique, and the European Commission (FP7, H2020) as well as a grant to participate in a symposium and contribute to the review of an article IPMDS, outside the submitted work. Jean-Denis Turc received an honorarium from Abbvie for a symposium outside the submitted work. Jean-Christophe Corvol served as a member of advisory boards for UCB, Biogen, Prevail Therapeutic, Idorsia, Sanofi, Ever Pharma, Denali, BrainEver, and Theranexus, and received an unrestricted grant from the Michael J. Fox Foundation outside the present work. Florence Tubach is head of the Centre de Pharmacoépidémiologie (Cephepi) of the Assistance Publique – Hôpitaux de Paris and of the Clinical Research Unit of Pitié-Salpêtrière Hospital, both these structures have received research funding, grants, and fees for consultant activities from a large number of pharmaceutical companies that have contributed indiscriminately to the salaries of its employees. Florence Tubach did not receive any personal remuneration from these companies.
Ethics approval
This is an observational study that did not involve any patients. All data were collected anonymously. In accordance with French law, no ethical approval is required.
Availability of Data and Material
The datasets generated during and analyzed during the current study are available from the corresponding author on reasonable request.
Authors Contributions
L-LM, OR, J-DT, ML-M, J-CC, and FT contributed to the study conception and design. Analyses were performed by HA and DL. The first draft of the manuscript was written by DL and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.
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Lastennet, D., Mariani, LL., Rascol, O. et al. Evaluation of Prescription Practices of Domperidone in Parkinson’s Disease: A Cross Sectional Study Among French Neurologists. CNS Drugs 34, 1267–1274 (2020). https://doi.org/10.1007/s40263-020-00774-w
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DOI: https://doi.org/10.1007/s40263-020-00774-w