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yet</button><a id="jr-fip-next" class="wsprkl btn" title="Jump to next match">▶</a></nav></nav></div><div id="jr-epub-interstitial" class="hidden"></div><div id="jr-content"><article data-type="main"><div class="main-content lit-style" itemscope="itemscope" itemtype="http://schema.org/CreativeWork"><div class="meta-content fm-sec"><div class="fm-sec"><h1 id="_NBK548175_"><span class="title" itemprop="name">Ropinirole</span></h1><p class="fm-aai"><a href="#_NBK548175_pubdet_">Publication Details</a></p></div></div><div class="body-content whole_rhythm" itemprop="text"><div id="Ropinirole.OVERVIEW"><h2 id="_Ropinirole_OVERVIEW_">OVERVIEW</h2><div id="Ropinirole.Introduction"><h3>Introduction</h3><p>Ropinirole is a selective dopamine receptor agonist used in the therapy of Parkinson disease. Ropinirole therapy is associated with low rate of transient serum enzyme elevations during treatment and has been implicated in rare cases of acute liver injury.</p></div><div id="Ropinirole.Background"><h3>Background</h3><p>Ropinirole (roe pin' i role") is a synthetic, nonergot derivative dopamine receptor agonist that has selective activity for the D2 class of dopamine receptors and little agonist activity for the D1 class. For this reason, ropinirole may be better tolerated than bromocriptine or pergolide, which act on both classes of dopamine receptors. Ropinirole was approved for use in the United States in 1997 for the therapy of symptomatic Parkinson disease. Indications were later expanded to include restless legs syndrome. Ropinirole is available in tablets of 0.25, 0.50, 1, 2, 3, 4 and 5 mg under the brand name of Requip. Ropinirole is typically initiated in low doses, with adjustment upwards based upon tolerance and clinical effects. In treatment of Parkinson disease, the typical dose of ropinirole is 3 to 6 mg daily in three divided doses, often but not always in combination with levodopa/carbidopa. Ropinirole can be initiated more quickly than bromocriptine or pergolide and does not cause the profound hypotension and nausea that are typical of the ergot derivatives. Rolinirole is also approved for use in restless legs syndrome, typically starting at 0.25 mg daily, 1 to 3 hours before bedtime, and increasing the dose slowly based upon tolerance and effect. Common side effects of ropinirole include somnolence, fatigue, vivid dreams, anxiety, confusion, depression, dizziness, headache and gastrointestinal upset, symptoms that are typical of dopaminergic stimulation.</p></div><div id="Ropinirole.Hepatotoxicity"><h3>Hepatotoxicity</h3><p>Ropinirole has been reported to cause serum aminotransferase or alkaline phosphatase elevations in a small proportion of patients, but these abnormalities are usually mild, asymptomatic and self-limiting even without dose adjustment. Ropinirole has been implicated in a small number of cases of acute liver injury, but the clinical characteristics and typical pattern of enzyme elevations has not been characterized. In one case report, the time to onset was 2 months and the pattern of liver enzyme elevations was mixed and associated with marked jaundice. Immunoallergic and autoimmune features were not present. The injury resolved within 2 months of stopping. Thus, ropinirole can cause acute, clinically apparent liver injury with jaundice, but it is rare.</p><p>Likelihood score: D (possible, rare cause of clinically apparent liver injury).</p></div><div id="Ropinirole.Mechanism_of_Injury"><h3>Mechanism of Injury</h3><p>Ropinirole is extensively metabolized in the liver, largely by the cytochrome P450 system (CYP 1A2) to inactive metabolites. Liver injury may be caused by production of a toxic or immunogenic intermediate of its metabolism.</p></div><div id="Ropinirole.Outcome_and_Management"><h3>Outcome and Management</h3><p>Instances of liver injury attributed to ropinirole have been mild to moderate and self-limiting. No instances of acute liver failure or chronic injury have been reported.</p><p>Drug Class: <a href="/books/n/livertox/AntiparkinsonAgents/?report=reader">Antiparkinson Agents</a></p><p>Other Drugs in the Subclass, Dopamine Receptor Agonists: <a href="/books/n/livertox/Apomorphine/?report=reader">Apomorphine</a>, <a href="/books/n/livertox/Bromocriptine/?report=reader">Bromocriptine</a>, <a href="/books/n/livertox/Pergolide/?report=reader">Pergolide</a>, <a href="/books/n/livertox/Pramipexole/?report=reader">Pramipexole</a>, <a href="/books/n/livertox/Rotigotine/?report=reader">Rotigotine</a></p></div></div><div id="Ropinirole.PRODUCT_INFORMATION"><h2 id="_Ropinirole_PRODUCT_INFORMATION_">PRODUCT INFORMATION</h2><div id="Ropinirole.BPI" class="box boxed-text-box whole_rhythm hide-overflow"><p>
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<b>REPRESENTATIVE TRADE NAMES</b>
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</p><p>Ropinirole – Generic, Requip®</p><p>
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<b>DRUG CLASS</b>
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</p><p>Antiparkinson Agents</p><p>
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<a href="https://dailymed.nlm.nih.gov/dailymed/search.cfm?labeltype=all&query=Ropinirole" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">COMPLETE LABELING</a>
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</p><p>Product labeling at DailyMed, National Library of Medicine, NIH</p></div></div><div id="Ropinirole.CHEMICAL_FORMULA_AND_STRUCTUR"><h2 id="_Ropinirole_CHEMICAL_FORMULA_AND_STRUCTUR_">CHEMICAL FORMULA AND STRUCTURE</h2><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figRopiniroleT1"><a href="/books/NBK548175/table/Ropinirole.T1/?report=objectonly" target="object" title="Table" class="img_link icnblk_img figpopup" rid-figpopup="figRopiniroleT1" rid-ob="figobRopiniroleT1"><img class="small-thumb" src="/books/NBK548175/table/Ropinirole.T1/?report=thumb" src-large="/books/NBK548175/table/Ropinirole.T1/?report=previmg" alt="Image " /></a><div class="icnblk_cntnt"><h4 id="Ropinirole.T1"><a href="/books/NBK548175/table/Ropinirole.T1/?report=objectonly" target="object" rid-ob="figobRopiniroleT1">Table</a></h4></div></div></div><div id="Ropinirole.REFERENCES"><h2 id="_Ropinirole_REFERENCES_">REFERENCES</h2><p>References updated: 21 July 2017</p><ul class="first-line-outdent"><li><div class="bk_ref" id="Ropinirole.R1">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.<div><i>(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).</i></div></div></li><li><div class="bk_ref" id="Ropinirole.R2">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.<div><i>(Review of hepatotoxicity of agents acting on the central nervous system).</i></div></div></li><li><div class="bk_ref" id="Ropinirole.R3">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.<div><i>(Textbook of pharmacology and therapeutics).</i></div></div></li><li><div class="bk_ref" id="Ropinirole.R4">Sethi KD, O'Brien CF, Hammerstad JP, Adler CH, Davis TL, Taylor RL, Sanchez-Ramos J, et al. Ropinirole for the treatment of early Parkinson disease: a 12-month experience. Ropinirole Study Group. Arch Neurol 1998; 55: 1211-6. [<a href="https://pubmed.ncbi.nlm.nih.gov/9740115" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 9740115</span></a>]<div><i>(147 patients with early Parkinson disease [not on levodopa] were randomized to receive ropinirole or placebo; no mention of ALT elevations or hepatic adverse events).</i></div></div></li><li><div class="bk_ref" id="Ropinirole.R5">Hauser RA, Molho E, Shale H, Pedder S, Dorflinger EE. A pilot evaluation of the tolerability, safety, and efficacy of tolcapone alone and in combination with oral selegiline in untreated Parkinson's disease patients. Tolcapone De Novo Study Group. Mov Disord 1998; 13: 643-7. [<a href="https://pubmed.ncbi.nlm.nih.gov/9686768" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 9686768</span></a>]<div><i>(Among 83 patients with Parkinson disease treated with tolcapone with or without selegiline for 8 weeks, ALT elevations occurred in 1 patient [2%] on tolcapone alone).</i></div></div></li><li><div class="bk_ref" id="Ropinirole.R6">Lambert D, Waters CH. Comparative tolerability of the newer generation antiparkinsonian agents. Drugs Aging 2000; 16: 55-65. [<a href="https://pubmed.ncbi.nlm.nih.gov/10733264" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 10733264</span></a>]<div><i>(Review of mechanism of action, tolerability and safety of selegiline, pramipexole, ropinirole, tolcapone and entacapone in Parkinson disease).</i></div></div></li><li><div class="bk_ref" id="Ropinirole.R7">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. [<a href="/pmc/articles/PMC3992250/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC3992250</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/20949552" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 20949552</span></a>]<div><i>(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). </i></div></div></li><li><div class="bk_ref" id="Ropinirole.R8">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. [<a href="https://pubmed.ncbi.nlm.nih.gov/20629075" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 20629075</span></a>]<div><i> (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).</i></div></div></li><li><div class="bk_ref" id="Ropinirole.R9">Navacerrada F, González-Alonso MR, Alonso-Navarro H, Pilo-de-la-Fuente B, Plaza-Nieto JF, Jiménez-Jiménez FJ. Liver toxicity possibly related with ropinirole use in the treatment of restless legs syndrome. Eur J Neurol 2011; 18: e65. [<a href="https://pubmed.ncbi.nlm.nih.gov/21199184" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 21199184</span></a>]<div><i>(68 year old woman developed jaundice 3 months after starting ropinirole for restless leg syndrome [bilirubin 11.1 mg/dL, ALT 2399 U/L, Alk P 2020 U/L], resolving within 2 months of stopping and no other cause was found).</i></div></div></li><li><div class="bk_ref" id="Ropinirole.R10">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. [<a href="https://pubmed.ncbi.nlm.nih.gov/23419359" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 23419359</span></a>]<div><i>(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).</i></div></div></li><li><div class="bk_ref" id="Ropinirole.R11">Drugs for Parkinson's disease. Treat Guidel Med Lett 2013; 11 (135): 101-6. [<a href="https://pubmed.ncbi.nlm.nih.gov/24165688" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 24165688</span></a>]<div><i>(Concise review of recommendations for therapy of Parkinson disease with description of mechanisms of action, efficacy and adverse events). </i></div></div></li><li><div class="bk_ref" id="Ropinirole.R12">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. [<a href="https://pubmed.ncbi.nlm.nih.gov/24552865" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 24552865</span></a>]<div><i>(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).</i></div></div></li><li><div class="bk_ref" id="Ropinirole.R13">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. [<a href="/pmc/articles/PMC4446235/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC4446235</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/25754159" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 25754159</span></a>]<div><i>(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).</i></div></div></li></ul></div><div id="bk_toc_contnr"></div></div></div><div class="fm-sec"><h2 id="_NBK548175_pubdet_">Publication Details</h2><h3>Publication History</h3><p class="small">Last Update: <span itemprop="dateModified">July 21, 2017</span>.</p><h3>Copyright</h3><div><div class="half_rhythm"><a href="/books/about/copyright/">Copyright Notice</a></div></div><h3>Publisher</h3><p><a href="https://www.niddk.nih.gov/" ref="pagearea=page-banner&targetsite=external&targetcat=link&targettype=publisher">National Institute of Diabetes and Digestive and Kidney Diseases</a>, Bethesda (MD)</p><h3>NLM Citation</h3><p>LiverTox: Clinical and Research Information on Drug-Induced Liver Injury [Internet]. Bethesda (MD): National Institute of Diabetes and Digestive and Kidney Diseases; 2012-. Ropinirole. [Updated 2017 Jul 21].<span class="bk_cite_avail"></span></p></div><div class="small-screen-prev"><a href="/books/n/livertox/Romosozumab/?report=reader"><svg xmlns="http://www.w3.org/2000/svg" viewBox="0 0 100 100" preserveAspectRatio="none"><path d="M75,30 c-80,60 -80,0 0,60 c-30,-60 -30,0 0,-60"></path><text x="20" y="28" textLength="60" style="font-size:25px">Prev</text></svg></a></div><div class="small-screen-next"><a href="/books/n/livertox/Rosiglitazone/?report=reader"><svg xmlns="http://www.w3.org/2000/svg" viewBox="0 0 100 100" preserveAspectRatio="none"><path d="M25,30c80,60 80,0 0,60 c30,-60 30,0 0,-60"></path><text x="20" y="28" textLength="60" style="font-size:25px">Next</text></svg></a></div></article><article data-type="boxed-text" id="figobRopiniroleBPI"><div id="Ropinirole.BPI" class="box boxed-text-box whole_rhythm hide-overflow"><p>
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<b>REPRESENTATIVE TRADE NAMES</b>
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</p><p>Ropinirole – Generic, Requip®</p><p>
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<b>DRUG CLASS</b>
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</p><p>Antiparkinson Agents</p><p>
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<a href="https://dailymed.nlm.nih.gov/dailymed/search.cfm?labeltype=all&query=Ropinirole" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">COMPLETE LABELING</a>
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</p><p>Product labeling at DailyMed, National Library of Medicine, NIH</p></div></article><article data-type="table-wrap" id="figobRopiniroleT1"><div id="Ropinirole.T1" class="table"><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK548175/table/Ropinirole.T1/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__Ropinirole.T1_lrgtbl__"><table><thead><tr><th id="hd_h_Ropinirole.T1_1_1_1_1" rowspan="1" colspan="1" style="vertical-align:top;">DRUG</th><th id="hd_h_Ropinirole.T1_1_1_1_2" rowspan="1" colspan="1" style="vertical-align:top;">CAS REGISTRY NUMBER</th><th id="hd_h_Ropinirole.T1_1_1_1_3" rowspan="1" colspan="1" style="vertical-align:top;">MOLECULAR FORMULA</th><th id="hd_h_Ropinirole.T1_1_1_1_4" rowspan="1" colspan="1" style="vertical-align:top;">STRUCTURE</th></tr></thead><tbody><tr><td headers="hd_h_Ropinirole.T1_1_1_1_1" rowspan="1" colspan="1" style="vertical-align:top;">Ropinirole</td><td headers="hd_h_Ropinirole.T1_1_1_1_2" rowspan="1" colspan="1" style="vertical-align:top;">
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<a href="https://pubchem.ncbi.nlm.nih.gov/substance/135028992" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">91374-20-8</a>
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</td><td headers="hd_h_Ropinirole.T1_1_1_1_3" rowspan="1" colspan="1" style="vertical-align:top;">C16-H24-N2-O.Cl-H</td><td headers="hd_h_Ropinirole.T1_1_1_1_4" rowspan="1" colspan="1" style="vertical-align:top;">
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<div class="graphic"><img src="/books/NBK548175/bin/Ropinirole_Structure.jpg" alt="Ropinirole Chemical Structure" /></div>
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