Rotigotine is a non-ergot dopamine receptor agonist used in the therapy of Parkinson disease and restless leg syndrome. Administered as a once daily transdermal patch, rotigotine has not been associated with serum enzyme elevations during treatment or with episodes of clinically apparent liver injury.
Rotigotine (roe tig' oh teen) is a synthetic dopamine agonist that is used to treat Parkinson disease and restless leg syndrome. Rotigotine is a nonselective agonist of dopamine receptors with highest affinity for the D3 class of receptors. It is structurally unrelated to ergot derivatives. Rotigotine is formulated as a transdermal patch which allows for once daily application and provides longer lasting and sustained plasma levels in comparison to other, oral non-ergot dopamine receptor agonists, such as ropinirole and pramipexole which are usually administered several times daily. In multiple placebo controlled clinical trials, rotigotine improved motor and daily activity scores in patients with Parkinson disease and in restless leg syndrome. Rotigotine was approved for this use in the United States in 2007. Current indications include both Parkinson disease and restless leg syndrome. Rotigotine is available in transdermal formulations which deliver 1, 2, 3, 4, 6 or 8 mg per 24 hours under the brand name Neupro. Rotigotine is typically initiated in doses of 2 mg per 24 hours in Parkinson disease and 1 to 3 mg per 24 hours for restless leg syndrome, with dose adjustments based upon tolerance and effects. Common side effects of rotigotine include application site reactions (erythema, pruritus) and systemic symptoms of nausea, dizziness, headache and somnolence – symptoms that are typical of dopaminergic stimulation. Weight gain and peripheral edema have also been described. Rare, but potentially severe adverse reactions include sudden sleep onset, sleep attacks, hallucinations, hypotension and syncope.
In multiple, controlled trials in Parkinson disease and restless leg syndrome, rotigotine transdermal patches were not associated with serum enzyme elevations, liver related severe adverse events or instances of clinically apparent liver injury. Since the approval and more wide scale use of rotigotine, there have been no published case reports of liver injury associated with its use and hepatotoxicity is not mentioned in the product label.
Likelihood score: E (unlikely cause of clinically apparent liver injury).
Mechanism of Liver Injury
Rotigotine is extensively metabolized in the liver acted upon by multiple cytochrome P450 isomers and conjugating enzymes. It has little or no effect on CYP isoenzyme activities and is not affected by drugs that inhibit or induce individual members of the microsomal enzyme system. The lack of hepatotoxicity of rotigotine may related to its transdermal formulation and relatively low daily dose (1 to 8 mg per 24 hours).
REPRESENTATIVE TRADE NAMES
Rotigotine – Neupro®
Product labeling at DailyMed, National Library of Medicine, NIH
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updated: 21 July 2017
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