Requip - Drug Monograph

Introduction

Requip (ropinirole hydrochloride) is a non-ergoline dopamine agonist medication primarily used in the treatment of Parkinson's disease and restless legs syndrome (RLS). Developed by GlaxoSmithKline, it received FDA approval for Parkinson's disease in 1997 and for RLS in 2005. Requip represents an important therapeutic option in the management of dopaminergic dysfunction.

Mechanism of Action

Ropinirole exerts its therapeutic effects through selective agonism of dopamine D2, D3, and D4 receptors in the striatum. Unlike ergot-derived dopamine agonists, it has minimal affinity for serotonin, adrenergic, or other neurotransmitter receptors. By stimulating postsynaptic dopamine receptors, it compensates for the depleted dopamine levels characteristic of Parkinson's disease. For restless legs syndrome, its mechanism is believed to involve modulation of dopaminergic pathways in the central nervous system that regulate motor function and sensory processing.

Indications

• Treatment of Parkinson's disease (idiopathic)
• Treatment of moderate-to-severe primary restless legs syndrome (RLS)
• May be used as monotherapy in early Parkinson's disease or as adjunctive therapy to levodopa

Dosage and Administration

• Initial dose: 0.25 mg three times daily
• Titration: Increase by 0.25 mg/dose every week to target dose of 1-3 mg three times daily
• Maximum dose: 24 mg/day

• Initial dose: 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 1 week
• Maximum dose: 4 mg daily

• Renal impairment: No dosage adjustment needed for mild-moderate impairment; use caution in severe impairment
• Hepatic impairment: Use caution and consider lower doses
• Elderly: No specific dosage adjustment required
• Pediatric: Safety and effectiveness not established

Pharmacokinetics

• Absorption: Rapidly absorbed with absolute bioavailability of 50%; Tmax 1-2 hours; food does not affect absorption
• Distribution: Volume of distribution 7 L/kg; 30-40% plasma protein binding
• Metabolism: Extensive hepatic metabolism primarily via CYP1A2; N-despropyl metabolite is inactive
• Elimination: Half-life approximately 6 hours; excreted primarily in urine (90%) as metabolites

Contraindications

• Hypersensitivity to ropinirole or any component of the formulation
• Concomitant use with antipsychotics that are dopamine antagonists

Warnings and Precautions

• Falling asleep during activities of daily living, including driving, which has resulted in accidents

• Orthostatic hypotension: Monitor especially during dose escalation
• Syncope: Can occur, especially during initial treatment
• Hallucinations/psychotic behavior: More common in elderly patients
• Impulse control disorders: Pathological gambling, hypersexuality, compulsive spending
• Withdrawal-emergent hyperpyrexia and confusion: Similar to neuroleptic malignant syndrome
• Melanoma: Patients with Parkinson's disease have higher risk; periodic skin examinations recommended
• Fibrotic complications: Although less common than with ergot derivatives, monitor for pulmonary, retroperitoneal, and cardiac fibrosis

Drug Interactions

• CYP1A2 inhibitors: Ciprofloxacin, fluvoxamine, verapamil (increase ropinirole concentrations)
• CYP1A2 inducers: Omeprazole, tobacco smoking (decrease ropinirole concentrations)
• Dopamine antagonists: Antipsychotics, metoclopramide (may diminish effectiveness)
• Estrogens: May increase ropinirole concentrations
• Sedatives/hypnotics: Enhanced sedative effects
• Alcohol: May potentiate cognitive and motor impairment

Adverse Effects

• Nausea (40%)
• Somnolence (40%)
• Dizziness (12%)
• Syncope (12%)
• vomiting (12%)
• Fatigue (8%)
• Orthostatic hypotension (6%)

• Myocardial infarction (rare)
• Cardiac arrhythmias
• Hallucinations
• Pathologic gambling and other impulse control disorders
• Neuroleptic malignant syndrome (upon withdrawal)
• Severe hypotension

Monitoring Parameters

• Blood pressure (sitting and standing) regularly, especially during dose titration
• Mental status and psychiatric symptoms
• Signs of impulse control disorders
• Daytime somnolence and sleep attacks
• Signs and symptoms of orthostatic hypotension
• Motor function and symptom control in Parkinson's disease
• RLS symptom improvement and sleep quality
• Skin examinations for melanoma detection
• Renal and hepatic function in patients with impairment

Patient Education

• Take medication exactly as prescribed; do not abruptly discontinue
• Be aware of potential for sudden sleepiness during daily activities
• Rise slowly from sitting/lying position to prevent dizziness
• Avoid alcohol while taking Requip
• Report any unusual urges (gambling, sexual, spending) to healthcare provider
• Inform all healthcare providers about Requip use before any new medications
• Use caution when driving or operating machinery until effects are known
• For RLS: Take 1-3 hours before bedtime
• Report any skin changes or new lesions to dermatologist
• Keep regular follow-up appointments for monitoring

References

1. FDA Prescribing Information: Requip (ropinirole hydrochloride) tablets 2. Pahwa R, Factor SA, Lyons KE, et al. Practice Parameter: treatment of Parkinson disease with motor fluctuations and dyskinesia (an evidence-based review). Neurology. 2006;66(7):983-995. 3. Trenkwalder C, Hening WA, Montagna P, et al. Treatment of restless legs syndrome: an evidence-based review and implications for clinical practice. Mov Disord. 2008;23(16):2267-2302. 4. National Institute for Health and Care Excellence. Parkinson's disease in adults: diagnosis and management. NICE guideline [NG71]. 2017. 5. Weintraub D, Koester J, Potenza MN, et al. Impulse control disorders in Parkinson disease: a cross-sectional study of 3090 patients. Arch Neurol. 2010;67(5):589-595. 6. Clinical Pharmacology [Internet]. Tampa (FL): Elsevier. Ropinirole; [updated 2023]. Available from: clinicalkey.com