Introduction
Ropinirole is a non-ergot dopamine agonist used primarily for the treatment of Parkinson's disease and restless legs syndrome. As a selective D2-like receptor agonist, it helps address the dopamine deficiency characteristic of Parkinson's disease while offering an alternative to levodopa therapy.
Mechanism of Action
Ropinirole exerts its therapeutic effects through selective agonism of dopamine D2, D3, and D4 receptors in the striatum. It activates postsynaptic dopamine receptors, mimicking the effects of endogenous dopamine. Unlike levodopa, ropinirole does not require conversion to become active and does not contribute to the formation of potentially toxic oxidative metabolites.
Indications
- Parkinson's disease: Monotherapy in early disease or adjunct therapy to levodopa
- Moderate to severe primary Restless Legs Syndrome (RLS)
- Off-label: antipsychotic-induced parkinsonism
Dosage and Administration
Parkinson's Disease:- Initial: 0.25 mg three times daily
- Titration: Increase by 0.25 mg/dose every week to target dose of 3-9 mg/day in divided doses
- Maximum: 24 mg/day
- Initial: 0.25 mg once daily 1-3 hours before bedtime
- Titration: Increase to 0.5 mg after 2 days, then 1 mg after 1 week, then 2 mg after 2 weeks
- Maximum: 4 mg daily
- Renal impairment: No dosage adjustment needed
- Hepatic impairment: Use caution in severe impairment
- Elderly: No specific dosage adjustment required
Pharmacokinetics
- Absorption: Rapidly absorbed, bioavailability ~50%, Tmax 1-2 hours
- Distribution: Vd ~7 L/kg, 30-40% plasma protein binding
- Metabolism: Extensive hepatic metabolism via CYP1A2
- Elimination: Half-life ~6 hours, primarily renal excretion (mostly metabolites)
Contraindications
- Hypersensitivity to ropinirole or any component of the formulation
- Concurrent use with antipsychotics that may diminish efficacy
Warnings and Precautions
- Sleep attacks: Sudden onset of sleep during activities
- Hypotension: Orthostatic hypotension common, especially during titration
- Impulse control disorders: Pathological gambling, hypersexuality, compulsive spending
- Hallucinations: More common in elderly and those taking higher doses
- Withdrawal symptoms: Dopamine agonist withdrawal syndrome possible with abrupt discontinuation
- Melanoma risk: Increased risk in Parkinson's patients; regular dermatologic monitoring recommended
Drug Interactions
- CYP1A2 inhibitors: Ciprofloxacin, fluvoxamine, verapamil (increase ropinirole levels)
- CYP1A2 inducers: Omeprazole, smoking (decrease ropinirole levels)
- Dopamine antagonists: Antipsychotics, metoclopramide (reduce efficacy)
- Antihypertensives: Additive hypotensive effects
- Ethanol: May enhance sedative effects
Adverse Effects
Common (>10%):- Nausea (40%)
- Dizziness (11-40%)
- Somnolence (11-40%)
- Syncope (1-10%)
- Hallucinations (5-8%)
- Impulse control disorders (up to 17%)
- Orthostatic hypotension
- Sudden sleep attacks
- Fibrotic complications (rare)
Monitoring Parameters
- Blood pressure (sitting and standing) during titration
- Mental status changes and psychiatric symptoms
- Daytime somnolence and sleep attacks
- Impulse control behaviors
- Parkinson's disease symptoms and progression
- Dermatologic examinations for melanoma screening
- Renal and hepatic function in patients with comorbidities
Patient Education
- Take with food to reduce nausea
- Rise slowly from sitting/lying position to prevent dizziness
- Report any unusual urges (gambling, sexual, spending) immediately
- Do not drive or operate machinery if experiencing drowsiness
- Avoid abrupt discontinuation
- Inform all healthcare providers about ropinirole use
- Regular skin examinations recommended
- Avoid alcohol during treatment
- Smoking may reduce medication effectiveness
References
1. FDA Prescribing Information: Requip (ropinirole hydrochloride) 2. Pahwa R, et al. Practice Parameter: treatment of Parkinson disease with motor fluctuations and dyskinesia. Neurology. 2006 3. Trenkwalder C, et al. Expert-based guidelines for the treatment of restless legs syndrome. Sleep Med. 2008 4. Stocchi F, et al. Ropinirole 24-hour prolonged release for Parkinson's disease. Expert Opin Pharmacother. 2007 5. Weintraub D, et al. Impulse control disorders in Parkinson disease. Arch Neurol. 2010 6. Clinical Pharmacology [Internet]. Tampa (FL): Gold Standard, Inc.; 2023