Rotigotine
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| Non-proprietary name | Rotigotine | ||||||||||||||||||
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(-) - ( S ) -6- [Propyl (2-thiophen-2-ylethyl) amino] -5,6,7,8-tetrahydronaphthalen-1-ol |
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| Molecular formula | C 19 H 25 NOS | ||||||||||||||||||
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| Molar mass | 315.47 g · mol -1 | ||||||||||||||||||
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| As far as possible and customary, SI units are used. Unless otherwise noted, the data given apply to standard conditions . | |||||||||||||||||||
Rotigotine (trade name Neupro ; Holder: UCB ) is a drug selected from the group of non- ergoline dopamine agonists , in the treatment of Parkinson's disease and idiopathic restless legs syndrome is used.
Clinical information
Rotigotine is used alone for the symptomatic treatment of Parkinson's disease in the early stages and in combination with levodopa in later stages of the disease . It can also be used to treat severe to moderate idiopathic Restless Legs Syndrome . Rotigotine is used once a day in the form of a transdermal patch from which the active ingredient is continuously released.
The effectiveness and tolerance of rotigotine have been shown in a number of clinical studies. Motor performance and activities of daily living in Parkinson's patients improved significantly under treatment with rotigotine.
Dosis, kind and Time of the Use
Through the transdermal application, the active ingredient rotigotine is supplied continuously over 24 hours. The resulting stable plasma level continuously stimulates the dopamine receptors in the brain, which improves the patient's mobility and reduces the occurrence of dyskinesia (gait disorders). The effect of the patch is independent of meals, gastroparesis or absorption disorders. Dosages from 1 mg to a maximum of 16 mg per 24 hours are possible. If the use of rotigotine has to be discontinued, the treatment should be gradually ended.
Contraindications
Rotigotine is not indicated in the case of known hypersensitivity to rotigotine.
unwanted effects
Typical dopaminergic side effects such as nausea, vomiting, dizziness, or drowsiness occur during treatment with rotigotine. Between one per thousand and one percent of the patients treated with rotigotine suffered from a chronic cough.
Simultaneous use with dopamine antagonists (e.g. neuroleptics ) may reduce the effect. If sedating drugs (e.g. benzodiazepines or antidepressants ) or alcohol are used at the same time, there is a risk of mutual reinforcement of the effects.
pregnancy and breast feeding period
There are no clinical data on the safety of rotigotine during pregnancy. Due to the prolactin-inhibiting effect of dopamine agonists, it is to be expected that milk production will be suppressed. Studies on rats have shown that rotigotine and its metabolites are excreted in breast milk. Since no corresponding data are available for humans, rotigotine should not be used during breastfeeding or breastfeeding should be stopped.
Pharmacological properties
Mechanism of action
Rotigotine is an agonist at D 3 / D 2 / D 1 receptors .
Pharmacokinetics
The active ingredient is continuously released after the transdermal patch is applied. The steady-state concentration is reached after one to two days. About 92% of rotigotine is bound to plasma proteins , the apparent volume of distribution is about 84 liters per kilogram. The bioavailability is about 37% with transdermal application. It fluctuates depending on the place of application, but this should not affect the therapeutic effectiveness. The transdermal delivery of rotigotine avoids the first-pass effect , effects from food and gastrointestinal diseases.
Rotigotine is partially metabolized by N -dealkylation, which is catalyzed by various cytochrome P450 isoforms, which in-vitro results suggest. The main metabolites are sulfates and glucuronide conjugates , which are formed by direct and secondary conjugation of rotigotine, as well as biologically inactive N -desalkyl metabolites.
toxicology
No cases of overdose were reported in clinical studies. The most likely adverse events are those related to the pharmacodynamic profile of a dopamine agonist, including nausea, vomiting, hypotension, involuntary movements, hallucinations , confusion, fits ( convulsions ), and other signs of central dopaminergic stimulation. There is no known antidote for the treatment of dopamine agonist overdose.
Trade names and dosage forms
Rotigotine is only administered transdermally using a patch; the dose of rotigotine is regulated by the size of the patch. Patches are available with 1, 2, 3, 4, 6 or 8 mg per 24 hours.
Development history
Rotigotine was synthesized at the University of Groningen in the 1980s and was first described as N-0437 in 1985. The development and marketing rights were transferred in 1998/99 from the US company Aderis to the German company Schwarz Pharma , which was transferred to the Belgian UCB SA in 2006.
The medicine was approved in the EU in February 2006 for the treatment of early-stage Parkinson's disease. In January 2007, EU approval for the later stages of the disease followed, and in May 2007, US approval for the early stages.
Due to technical problems in the manufacture of the patch, the US market was recalled in March 2008 , while patients in the EU were supplied via a cold chain .
In August 2008, the European Commission approved the treatment for the symptomatic treatment of moderate to severe idiopathic Restless Legs Syndrome in adults, and Neupro has been prescribable for this indication since June 2009.
At the beginning of April 2012, the FDA granted renewed approval for the American market.
Web links
- Information on Neupro on the European Medicines Agency website
Individual evidence
- ↑ There is not yet a harmonized classification for this substance . A labeling of (6S) -6- [propyl (2-thiophen-2-ylethyl) amino] -5,6,7,8-tetrahydronaphthalen-1-ol in the Classification and Labeling Inventory is shown, which is derived from a self-classification by the distributor European Chemicals Agency (ECHA), accessed July 12, 2020.
- ^ Parkinson Study Group: A Controlled Trial of Rotigotine Monotherapy in Early Parkinson's Disease . In: Arch Neurol , 2003, 60, pp. 1721-1728. PMID 14676046
- ^ RL Watts, J Jankovic, C Waters et al .: Randomized, blind, controlled trial of transdermal rotigotine in early Parkinson disease . In: Neurology , 2007, 68, pp. 272-276, PMID 17202432 .
- ↑ AS Horn, P Tepper, J Van der Weide et al .: Synthesis and radioreceptor binding activity of N-0437, a new, extremely potent and selective D2 dopamine receptor agonist . In: Pharm Weekbl Sci , 1985, 7, pp. 208-211, PMID 2933633 .
- ↑ UCB advises US physicians to down-titrate patients on Neupro ® in view of out-of-stock situation in the US . (PDF; 44 kB) Press release UCB SA, March 20, 2008; Retrieved August 2, 2008.
- ↑ UCB to implement full cold-chain for Neupro ® (PDF; 39 kB) Press release UCB SA, June 4, 2008; Retrieved August 2, 2008.
- ↑ Rote-Hand-Brief on Neupro® transdermal patches: Information on storage. BfArM , June 12, 2008, accessed April 29, 2017 .
