Usage
- Ropinirole is prescribed for the treatment of Parkinson’s Disease (PD) and moderate-to-severe idiopathic Restless Legs Syndrome (RLS), also known as Willis-Ekbom Disease. In Parkinson’s disease, it can be used as monotherapy or in combination with levodopa.
- Pharmacological classification: Non-ergot dopamine agonist.
- Ropinirole acts as a dopamine D2 and D3 receptor agonist, mimicking the effects of dopamine in the brain. This helps improve motor control and reduce the symptoms of PD and RLS.
Alternate Names
- No widely used alternate generic names.
- Brand Names: Requip, Requip XL, Ropinirole Hydrochloride.
How It Works
- Pharmacodynamics: Ropinirole stimulates dopamine receptors in the brain, particularly D2 and D3 receptors, leading to improved motor control and reduced RLS symptoms.
- Pharmacokinetics:
- Absorption: Well-absorbed orally. Food, especially high-fat meals, can delay absorption and reduce peak plasma concentration, though overall absorption is unaffected.
- Metabolism: Extensively metabolized in the liver, primarily by CYP1A2, into inactive metabolites.
- Elimination: Primarily eliminated via renal excretion. Elimination half-life is approximately 6 hours.
- Mode of Action: Ropinirole directly activates postsynaptic dopamine receptors, similar to dopamine’s action. This enhances dopaminergic neurotransmission in the brain regions affected by PD and RLS.
- Receptor Binding: Agonist at D2 and D3 receptors, with higher affinity for D3.
- Elimination pathways: Primarily renal excretion of metabolites; hepatic metabolism by CYP1A2 plays a crucial role.
Dosage
Standard Dosage
Adults:
Parkinson’s Disease:
- Immediate-Release Tablets:
- Initial: 0.25 mg orally three times daily.
- Titrate weekly based on response and tolerability: Week 2: 0.5 mg TID; Week 3: 0.75 mg TID; Week 4: 1 mg TID.
- After week 4: Increase by 1.5 mg/day weekly up to 9 mg/day, then increase by 3 mg/day weekly up to a maximum of 24 mg/day.
- Extended-Release Tablets:
- Initial: 2 mg orally once daily for 1-2 weeks.
- Increase by 2 mg/day at weekly (or longer) intervals, up to a maximum of 24 mg/day.
Restless Legs Syndrome:
- Immediate-Release Tablets:
- Initial: 0.25 mg orally once daily, 1-3 hours before bedtime.
- After 2 days: Increase to 0.5 mg once daily.
- At the end of week 1: Increase to 1 mg once daily.
- Titrate weekly by 0.5 mg/day up to a maximum of 4 mg/day.
Children:
- Not recommended for use in children under 18 years old due to lack of safety and efficacy data.
Special Cases:
- Elderly Patients: Titrate cautiously as clearance may be reduced. Monitor for increased sensitivity to side effects, especially hallucinations. No initial dose adjustment is required.
- Patients with Renal Impairment:
- Moderate impairment (CrCl 30-50 ml/min): No dose adjustment necessary.
- End-stage renal disease (ESRD) on hemodialysis:
- Parkinson’s disease: Start at 0.25 mg TID (immediate-release) or 2 mg once daily (extended-release). Maximum dose: 18 mg/day.
- RLS: Start at 0.25 mg once daily (immediate-release). Maximum dose: 3 mg/day.
- Patients with Hepatic Dysfunction: Titrate cautiously as plasma levels may be higher. Monitor closely.
- Patients with Comorbid Conditions: Exercise caution in patients with heart disease, high blood pressure, or low blood pressure.
Clinical Use Cases
Ropinirole is not indicated for intubation, surgical procedures, mechanical ventilation, intensive care unit (ICU) use, or emergency situations. It specifically targets the symptoms of Parkinson’s Disease and Restless Legs Syndrome.
Dosage Adjustments:
Titration should be based on individual patient response and tolerability. Consider renal and hepatic function, as well as comorbid conditions, when adjusting the dose. Gradual dose reduction is recommended when discontinuing ropinirole to avoid withdrawal symptoms.
Side Effects
Common Side Effects:
Nausea, dizziness, somnolence, hallucinations, orthostatic hypotension, edema, constipation, vomiting, fatigue.
Rare but Serious Side Effects:
Sudden sleep onset, impulse control disorders (e.g., compulsive gambling, shopping, eating), malignant melanoma (potential risk), severe allergic reactions.
Long-Term Effects:
Augmentation of RLS symptoms (symptoms worsening or appearing earlier in the day), impulse control disorders.
Adverse Drug Reactions (ADR):
Severe hypotension, syncope, allergic reactions (angioedema, anaphylaxis), hallucinations, psychosis, impulse control disorders.
Contraindications
- Hypersensitivity to ropinirole.
Drug Interactions
- CYP1A2 inhibitors: (e.g., ciprofloxacin, fluvoxamine) can increase ropinirole levels. Dose adjustment may be necessary.
- CYP1A2 inducers: (e.g., smoking) can decrease ropinirole levels.
- Estrogens: May require dose adjustments.
- CNS depressants: (e.g., alcohol, benzodiazepines) can additive sedative effects.
- Antihypertensives: May enhance hypotensive effects.
Pregnancy and Breastfeeding
- Pregnancy Safety Category: C (Animal studies show risk, human studies inadequate). Use only if the potential benefit outweighs the risk to the fetus.
- Breastfeeding: Ropinirole is excreted in breast milk. Avoid using during breastfeeding or discontinue breastfeeding.
Drug Profile Summary
- Mechanism of Action: Dopamine D2 and D3 receptor agonist.
- Side Effects: Nausea, dizziness, somnolence, hallucinations, orthostatic hypotension, impulse control disorders.
- Contraindications: Hypersensitivity.
- Drug Interactions: CYP1A2 inhibitors/inducers, estrogens, CNS depressants.
- Pregnancy & Breastfeeding: Category C; avoid during breastfeeding.
- Dosage: Titrate based on individual response and tolerability; see detailed dosage guidelines above.
- Monitoring Parameters: Blood pressure, motor symptoms, RLS symptoms, signs of impulse control disorders.
Popular Combinations
- Levodopa in advanced Parkinson’s disease.
Precautions
- General Precautions: Monitor blood pressure, assess for impulse control disorders and compulsive behaviors.
- Specific Populations: See detailed dosage guidelines for elderly patients, patients with renal/hepatic impairment, and pregnant/breastfeeding women.
- Lifestyle Considerations: Alcohol can increase sedation. Smoking may reduce ropinirole levels.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Ropinirole?
A: See the detailed dosage section above, which covers dosing for adults with Parkinson’s disease and Restless Legs Syndrome, as well as special considerations for various patient populations.
Q2: What are the common side effects of Ropinirole?
A: Common side effects include nausea, dizziness, somnolence, hallucinations, and orthostatic hypotension.
Q3: How does Ropinirole work?
A: Ropinirole acts as a dopamine agonist, stimulating dopamine receptors in the brain.
Q4: Can Ropinirole be used during pregnancy?
A: Pregnancy Category C. Use only if the potential benefit justifies the potential risk to the fetus.
Q5: Are there any drug interactions with Ropinirole?
A: Yes. CYP1A2 inhibitors, CYP1A2 inducers, estrogens, and CNS depressants can interact with ropinirole.
Q6: What should I monitor in patients taking Ropinirole?
A: Monitor blood pressure, motor symptoms, RLS symptoms, and any signs of impulse control disorders or compulsive behaviors.
Q7: What is the difference between Requip and Requip XL?
A: Requip is the immediate-release formulation, while Requip XL is the extended-release formulation.
Q8: How should I discontinue Ropinirole?
A: Gradually taper the dose over 7 days to avoid withdrawal symptoms.
Q9: Can Ropinirole be used in children?
A: No, it is not recommended for use in children under 18.
A: Augmentation is a worsening of RLS symptoms, where they become more severe, start earlier in the day, or spread to other body parts. It can be a long-term side effect of dopamine agonists like ropinirole.
