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.
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.
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.
Likelihood score: D (possible, rare cause of clinically apparent liver injury).
Mechanism of Injury
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.
Outcome and Management
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.
REPRESENTATIVE TRADE NAMES
Ropinirole – Generic, Requip®
Product labeling at DailyMed, National Library of Medicine, NIH
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References updated: 21 July 2017
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