Drug products: Derinik, Mirapexin, MIRAPEXIN®, Oprymea, Oprymea®, Pramipexol Aurobindo, Pramipexol Sandoz, Pramipexol STADA, Pramipexol Teva Pharma, Pramipexol Zentiva, Pramipexole Accord, Pramipexole Bluefish, Pramipexole Orion, Pramipexole Sandoz, Pramipexole Teva, SIFROL, Sifrol®, SIFROL®
ATC code: N04BC05
Substances: pramipexole, pramipexole dihydrochloride monohydrate
Clinical trials conducted by the pharmaceutical company have not demonstrated any difference in effect or adverse events between men and women with Parkinson’s disease treated with pramipexol. In patients treated for RLS (Restless Legs Syndrome) nausea and fatigue has been more frequently reported in women.
The reported incidence and prevalence of Parkinson’s disease (PD) is slightly higher in men than in women. It seems that men develop PD earlier in life compared to women. Several possible explanations behind these sex differences have been suggested; the protective role of estrogens in premenopausal women, and different profiles of risk factors (environmental and/or genetic). Sex differences in clinical presentations of PD have also been reported. Since the activities of daily living might differ between men and women with PD, different treatment strategies can be recommended to men and women with PD .
Pharmacokinetics and dosing
In a pharmacokinetic study in healthy volunteers (8 men, 8 women), AUC and Cmax of pramipexol were significantly higher in women for the dose 1.5 mg. The mean creatinine clearance was lower in women than in men (80.9 ±15.6 vs. 112 ±12.8 mL/min/1.73 m2). However, women had higher mean age in this study, and aging leads to a decline in glomerular filtration rate. Also, the normal range of glomerular filtration rate, measured by inulin clearance, is lower for women. Therefore, the influence of patient’s sex could not be distinguished from the influence of age and the resulting reduced creatinine clearance . Pramipexole clearance has been shown to be about 30% lower in women than in men, but this difference can be accounted for by differences in body weight. There was no difference in half-life between men and women .
Therapy with pramipexole should be initiated at a low dose and gradually titrated upwards according to clinical tolerability to obtain the optimum therapeutic effect. It is not necessary to adjust the initial dose based on patient’s sex .
Clinical studies conducted by the pharmaceutical company found no difference between men and women in effect of pramipexol in Parkinson’s Disease . No other published studies with a clinically relevant sex analysis regarding the effects of pramipexole have been found.
The increased risk of impulse control disorder with use of dopamine agonists is well known [2-6]. One observational study on dopamine agonists (n=642, approx. 2/3 men) reports a higher frequency of impulse control disorder in men compared to women in patients using dopamine agonists .However, in a transversal study of patients on a single nonergolinic dopamine agonist (pramipexole, ropinirole, or rotigotine) (145 men, 88 women) no difference in risk between men and women was reported .
Reproductive health issues
Regarding teratogenic aspects, please consult Janusmed Drugs and Birth Defects (in Swedish, Janusmed fosterpåverkan).
Date of litterature search: 2019-11-07
- Georgiev D, Hamberg K, Hariz M, Forsgren L, Hariz GM. Gender differences in Parkinson's disease: A clinical perspective. Acta Neurol Scand. 2017;136(6):570-584. PubMed
- Wright CE, Sisson TL, Ichhpurani AK, Peters GR. Steady-state pharmacokinetic properties of pramipexole in healthy volunteers. J Clin Pharmacol. 1997;37:520-5. PubMed
- Mirapex (pramipexole dihydrochloride). DailyMed [www]. US National Library of Medicine. [updated 2018-05-01, cited 2019-11-07]. länk
- Läkemedelsstatistik. Stockholm: Socialstyrelsen. 2019 [cited 2020-03-10.] länk
- Weintraub D, Siderowf AD, Potenza MN, Goveas J, Morales KH, Duda JE, Moberg PJ, Stern MB. Association of dopamine agonist use with impulse control disorders in Parkinson disease. Arch Neurol. 2006;63(7):969-73. länk
- Schreglmann SR, Gantenbein AR, Eisele G, Baumann CR. Transdermal rotigotine causes impulse control disorders in patients with restless legs syndrome. Parkinsonism Relat Disord. 2012;18:207-9. PubMed
- Carrière N, Kreisler A, Dujardin K, Destée A, Defebvre L. [Impulse control disorders in Parkinson's disease: A cohort of 35 patients]. Rev Neurol (Paris). 2012;168:143-51. PubMed
- Poletti M, Logi C, Lucetti C, Del Dotto P, Baldacci F, Vergallo A, Ulivi M, Del Sarto S, Rossi G, Ceravolo R, Bonuccelli U. A single-center, cross-sectional prevalence study of impulse control disorders in Parkinson disease: association with dopaminergic drugs. J Clin Psychopharmacol. 2013;33(5):691-4. PubMed
- Garcia-Ruiz, P J Martinez Castrillo JC, Alonso-Canovas A, Herranz Barcenas A, Vela L, Sanchez Alonso P, Mata M, Olmedilla Gonzalez N, Mahillo Fernandez I. Impulse control disorder in patients with Parkinson's disease under dopamine agonist therapy: a multicentre study. J Neurol Neurosurg Psychiatry. 2014;85(8):840-4. länk
Reviewed by: Mia von Euler, Diana Rydberg
Approved by: Karin Schenck-Gustafsson