OVERVIEW

PRODUCT INFORMATION

CHEMICAL FORMULA AND STRUCTURE

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DRUG	CAS REGISTRY NUMBER	MOLECULAR FORMULA	STRUCTURE
Rotigotine	99755-59-6	C19-H25-N-O-S

REFERENCES

References updated: 21 July 2017

• Zimmerman HJ. Antiparkinsonism drugs. In, Zimmerman HJ. Hepatotoxicity: the adverse effects of drugs and other chemicals on the liver. 2nd ed. Philadelphia: Lippincott, 1999, pp. 715-7.

  (Expert review of hepatotoxicity published in 1999; among anticholinergic agents, "only trihexyphenidyl has been incriminated in hepatic injury"; other antiparkinsonism drugs discussed include levodopa, lergotrile [no longer available], pergolide and bromocriptine, but not ropinirole).
• Larrey D, Ripault MP. Hepatotoxicity of psychotropic drugs and drugs of abuse. In, Kaplowitz N, DeLeve LD, eds. Drug-induced liver disease. 3rd ed. Amsterdam: Elsevier Inc, 2013, pp. 443-62.

  (Review of hepatotoxicity of agents acting on the central nervous system).
• Standaert DG, Roberson ED. Treatment of central nervous system degenerative disorders. In, Brunton LL, Chabner BA, Knollman BC, eds. Goodman & Gilman’s the pharmacological basis of therapeutics. 12th ed. New York: McGraw-Hill, 2011, pp. 609-28.

  (Textbook of pharmacology and therapeutics).
• Lambert D, Waters CH. Comparative tolerability of the newer generation antiparkinsonian agents. Drugs Aging 2000; 16: 55-65. [PubMed: 10733264]

  (Review of mechanism of action, tolerability and safety of selegiline, pramipexole, ropinirole, tolcapone and entacapone in Parkinson disease).
• Reuben A, Koch DG, Lee WM; Acute Liver Failure Study Group. Drug-induced acute liver failure: results of a U.S. multicenter, prospective study. Hepatology 2010; 52: 2065-76. [PMC free article: PMC3992250] [PubMed: 20949552]

  (Among 1198 patients with acute liver failure enrolled in a US prospective study between 1998 and 2007, 133 were attributed to drug induced liver injury, but none were attributed to agents used for Parkinson disease).
• Giladi N, Boroojerdi B, Korczyn AD, Burn DJ, Clarke CE, Schapira AH; SP513 investigators. Rotigotine transdermal patch in early Parkinson's disease: a randomized, double-blind, controlled study versus placebo and ropinirole. Mov Disord 2007; 22: 2398-404. [PubMed: 17935234]

  (Among 561 patients with early Parkinson disease treated with rotigotine, ropinirole or placebo for 24 weeks, rates of response were 52%, 68% and 30% and side effects that were more common with rotigotine than placebo were application site reactions [38% vs 7%], nausea [29% vs 16%], vomiting [12% vs 3%], dizziness [14% vs 10%], and sleep attacks [3% vs 0]; no mention of ALT elevations or liver related severe adverse events).
• Transdermal rotigotine (Neupro) for Parkinson's disease. Med Lett Drugs Ther 2007; 49 (1268): 69-70. [PubMed: 17712291]

  (Concise review of the mechanism of action, efficacy, safety and costs of transdermal rotigotine shortly after its approval in the US; mentions side effects of nausea, dizziness and somnolence, but not serum ALT elevations or hepatotoxicity).
• LeWitt PA, Lyons KE, Pahwa R; SP 650 Study Group. Advanced Parkinson disease treated with rotigotine transdermal system: PREFER Study. Neurology 2007; 68: 1262-7. [PubMed: 17438216]

  (Among 351 patients with advanced Parkinson disease treated with transdermal rotigotine [8 or 12 mg/234 hours] or placebo for 25 weeks, there were greater decreases in “off” time with rotigotine; side effects were those typical of dopaminergic stimulation, and “clinical laboratory test results…revealed no tendencies for the study medication to cause toxicity”).
• 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: 272-6. [PubMed: 17202432]

  (Among 277 patients with early Parkinson disease treated with transdermal rotigotine or placebo for 6 months, those on rotigotine had more improvement in motor activity, but also were more likely to have nausea, vomiting, diarrhea, somnolence and insomnia; no mention of ALT elevations or hepatotoxicity).
• Oertel WH, Benes H, Garcia-Borreguero D, Geisler P, Högl B, Saletu B, Trenkwalder C, et al; Rotigotine SP 709 Study Group. Efficacy of rotigotine transdermal system in severe restless legs syndrome: a randomized, double-blind, placebo-controlled, six-week dose-finding trial in Europe. Sleep Med 2008; 9: 228-39. [PubMed: 17553743]

  (Among 341 patients with restless leg syndrome treated with rotigotine patches [5 doses] or placebo for 8 weeks, there were slight improvements in symptoms with rotigotine therapy, while side effects included application site reactions [37%], nausea, vomiting and dizziness; but “no clinically relevant changes” in clinical chemistry results were observed).
• Hening WA, Allen RP, Ondo WG, Walters AS, Winkelman JW, Becker P, Bogan R, et al; SP792 Study Group. Rotigotine improves restless legs syndrome: a 6-month randomized, double-blind, placebo-controlled trial in the United States. Mov Disord 2010; 25: 1675-83. [PubMed: 20629075]

  (Among 505 patients with restless leg syndrome treated with one of 4 doses of transdermal rotigotine or placebo for 6 months, symptom scores improved with higher doses [2 or 3 mg/24 hours] and side effects included application site reactions, nausea, somnolence, headache and insomnia, but there were no liver related serious adverse events).
• Björnsson ES, Bergmann OM, Björnsson HK, Kvaran RB, Olafsson S. Incidence, presentation, and outcomes in patients with drug-induced liver injury in the general population of Iceland. Gastroenterology 2013; 144: 1419-25,1425. [PubMed: 23419359]

  (In a population based study of drug induced liver injury from Iceland, 96 cases were identified over a 2 year period, but none of the 96 were attributed to an agent used to treat Parkinson disease).
• Drugs for Parkinson's disease. Treat Guidel Med Lett 2013; 11 (135): 101-6. [PubMed: 24165688]

  (Concise review of recommendations for therapy of Parkinson disease with description of mechanisms of action, efficacy and adverse events).
• Hernández N, Bessone F, Sánchez A, di Pace M, Brahm J, Zapata R, A Chirino R, et al. Profile of idiosyncratic drug induced liver injury in Latin America: an analysis of published reports. Ann Hepatol 2014; 13: 231-9. [PubMed: 24552865]

  (Among 176 reports of drug induced liver injury from Latin America published between 1996 and 2012, none were attributed to an agent to treat Parkinson disease).
• McAfee DA, Hadgraft J, Lane ME. Rotigotine: the first new chemical entity for transdermal drug delivery. Eur J Pharm Biopharm 2014; 88: 586-93. [PubMed: 25173087]

  (Review of the development, pharmacokinetics, clinical efficacy of transdermal formulations of rotigotine mentions that the main adverse reactions are application site reactions, nausea and somnolence; no mention of serum enzyme elevations or hepatotoxicity).
• Nomoto M, Mizuno Y, Kondo T, Hasegawa K, Murata M, Takeuchi M, Ikeda J, et al. Transdermal rotigotine in advanced Parkinson's disease: a randomized, double-blind, placebo-controlled trial. J Neurol 2014; 261: 1887-93. [PubMed: 25022939]

  (Among 172 Japanese patients with advanced Parkinson disease treated with rotigotine [up to 16 mg/24 hours] or placebo for 14 weeks, symptoms improved more with rotigotine than placebo treatment and adverse events included application site reactions, nausea and somnolence; there were no liver related serious adverse events).
• Chalasani N, Bonkovsky HL, Fontana R, Lee W, Stolz A, Talwalkar J, Reddy KR, et al.; United States Drug Induced Liver Injury Network. Features and outcomes of 899 patients with drug-induced liver injury: The DILIN Prospective Study. Gastroenterology 2015; 148: 1340-52. [PMC free article: PMC4446235] [PubMed: 25754159]

  (Among 899 cases of drug induced liver injury from the US enrolled in a prospective database between 2004 and 2012, none were attributed to an agent used to treat Parkinson disease).