Rotigotine

(USAN, rINN)
Synonyms: N-0923; Rotigotina; Rotigotinum; SPM-962. (−)-(S)-5,6,7,8-Tetrahydro-6-{propyl[2-(2-thienyl)ethyl]amino}-1-naphthol.
Cyrillic synonym: Ротиготин.

💊 Chemical information

Chemical formula: C19H25NOS = 315.5.
CAS — 99755-59-6 (rotigotine); 125572-93-2 (rotigotine hydrochloride).
ATC — N04BC09.
ATC Vet — QN04BC09.

💊 Adverse Effects and Precautions

As for Bromocriptine. Reactions may occur at the site of application and are usually mild or moderate in intensity. The site should be rotated on a daily basis and the same site should not be used within 14 days. Licensed product information recommends that rotigotine should be used with caution in patients with severe hepatic impairment and reduced doses may be necessary in cases of worsening impairment; however, this is based on a lack of evidence in such patients.

💊 Interactions

Since it is a dopamine agonist, rotigotine may share some of the pharmacological interactions of bromocriptine. Caution is advised when other sedating drugs or alcohol are used with rotigotine because of possible additive effects.

💊 Pharmacokinetics

Rotigotine has poor oral bioavailability as it undergoes extensive first-pass metabolism via glucuronidation in the gut wall and liver. Peak plasma concentrations are achieved 24 hours after transdermal application. Steady-state concentrations are reached after 24 to 48 hours of continuous daily application. It undergoes N-dealkylation and conjugation to form inactive metabolites. Rotigotine is excreted mainly in the urine and about 23% appears in the faeces. The elimination half-life is 5 to 7 hours. It is distributed into milk of rats.

💊 Uses and Administration

Rotigotine is a non-ergot dopamine D2-agonist with similar actions to those of bromocriptine, but in contrast to bromocriptine (a dopamine D2-agonist) it also has agonist properties at D1 and D3 receptors. It is used as monotherapy in the management of Parkinson’s disease, mainly in the early stage. It may also be used as an adjunct to levodopa therapy. Rotigotine is given as transdermal patches delivering amounts ranging from 2 to 8 mg per 24 hours. When given as monotherapy, the initial dose is 2 mg daily, increased in weekly steps of 2 mg if necessary to a maximum of 8 mg daily. Rotigotine may also be used as adjunctive therapy with levodopa in an initial dose of 4 mg daily, increased in weekly steps of 2 mg if necessary, to a maximum of 16 mg daily. Patches are applied once daily and should be replaced every 24 hours with the new patch being applied to a different site. Treatment with rotigotine should be withdrawn gradually; the daily dose should be reduced in steps of 2 mg every other day until complete withdrawal is achieved. Rotigotine is also being studied as a transdermal preparation in the treatment of restless legs syndrome.
1. The Parkinson Study Group. A controlled trial of rotigotine monotherapy in early Parkinson’s disease. Arch Neurol 2003; 60: 1721–8
2. Stiasny-Kolster K, et al. Patch application of the dopamine agonist rotigotine to patients with moderate to advanced stages of restless legs syndrome: a double-blind, placebo-controlled pilot study. Mov Disord 2004; 19: 1432–8
3. Poewe W, Leussi F. Clinical studies with transdermal rotigotine in early Parkinson’s disease. Neurology 2005; 65 (suppl 1): S11–S14. Correction. ibid.; 1328
4. Watts RL, et al. Randomized, blind, controlled trial of transdermal rotigotine in early Parkinson disease. Neurology 2007; 68: 272–6. Correction. ibid.; 69: 617
5. Splinter MY. Rotigotine: transdermal dopamine agonist treatment of Parkinson’s disease and restless legs syndrome. Ann Pharmacother 2007; 41: 285–95
6. LeWitt PA, et al. Advanced Parkinson disease treated with rotigotine transdermal system: PREFER Study. Neurology 2007; 68: 1262–7.

💊 Preparations

Proprietary Preparations

Cz.: Neupro; Gr.: Neupro; Pol.: Neupro; Port.: Neupro; UK: Neupro; USA: Neupro†.
Published November 25, 2018.