Ropinirole

Generic Name

Ropinirole hydrochloride

Brand Names

Requip

Requip XL

Ropark

Ropitor

Ropinal

Adartrel (UK)

Generic ropinirole is widely available globally in immediate-release (IR) and extended-release (ER) formulations

Drug Class

Non-ergot dopamine agonist

Antiparkinsonian agent

Restless Legs Syndrome (RLS) treatment

Dopaminergic agent

Mechanism of Action

Ropinirole is a selective dopamine D₂ receptor agonist with moderate activity at D₃ and D₄ receptors

It mimics the action of dopamine in the striatum and substantia nigra of the brain

It helps restore dopaminergic tone in patients with Parkinson’s disease by stimulating post-synaptic dopamine receptors

In Restless Legs Syndrome, its effect is believed to stem from enhanced dopaminergic transmission within spinal and central nervous system pathways involved in sensory and motor control

Unlike levodopa, it does not require enzymatic conversion and does not depend on endogenous dopamine levels

Indications

Approved Indications

Parkinson’s disease (idiopathic): monotherapy or adjunct to levodopa in patients experiencing 'wearing-off' symptoms

Moderate-to-severe primary Restless Legs Syndrome (RLS)

Off-Label Uses

Periodic limb movement disorder (PLMD)

Drug-induced parkinsonism (e.g., antipsychotic-induced)

Treatment-resistant depression (as augmentation in select cases)

Tardive dyskinesia (investigational use)

Dosage and Administration

For Parkinson’s Disease

Immediate-Release (IR)

Initial: 0.25 mg three times daily

Increase weekly by 0.25 mg per dose for Week 2 (total 2.25 mg/day)

Subsequent titration: increase by 1.5 mg/day in divided doses every week

Typical effective dose: 3 mg/day to 9 mg/day

Max dose: 24 mg/day (in 3 divided doses)

Extended-Release (ER)

Start: 2 mg once daily

Titrate at weekly intervals by 2 mg/day

Typical range: 4–8 mg/day

Max: 24 mg/day

Switching from IR to ER requires calculation of total daily IR dose and conversion to nearest ER dose

For Restless Legs Syndrome

Immediate-Release Only

Initial: 0.25 mg once daily 1–3 hours before bedtime

Increase to 0.5 mg on day 3 and 1 mg at end of week 1

Subsequent weekly titration to max of 4 mg/day based on response

Usual effective range: 0.5–2 mg/day

Extended-release formulation not approved for RLS

Administration

May be taken with or without food

Food reduces risk of nausea

ER tablets should not be crushed, chewed, or divided

IR tablets are taken multiple times per day in PD, once daily for RLS

Pharmacokinetics

Absorption

Well absorbed orally

Bioavailability ~55%

Peak plasma levels in 1–2 hours (IR), 6–10 hours (ER)

Distribution

Widely distributed

Volume of distribution ~7.5 L/kg

10–40% protein-bound

Metabolism

Extensively metabolized by CYP1A2 to inactive metabolites

Also undergoes glucuronidation

Minimal interaction with CYP3A4 or CYP2D6

Elimination

Mainly via urine (60% as metabolites)

Feces (~20%)

Half-life: 6 hours (IR), 8–12 hours (ER)

Clearance reduced in elderly and hepatic impairment

Contraindications

Known hypersensitivity to ropinirole or any tablet component

Use with caution in patients with severe cardiovascular disease or significant psychiatric illness

Warnings and Precautions

Dyskinesia

May increase involuntary movements when used with levodopa

Adjust levodopa dose as needed

Hallucinations and Psychosis

Visual hallucinations more common in elderly

Risk increases when combined with other dopaminergic drugs

Use caution in patients with underlying psychiatric disorders

Impulse Control Disorders

Gambling, hypersexuality, binge eating, compulsive shopping reported

Monitor patients closely

Consider dose reduction or discontinuation if behavior emerges

Orthostatic Hypotension

Can cause dizziness, syncope, or falls

Monitor blood pressure during initiation and titration

Caution in patients with cardiovascular disease

Sudden Sleep Attacks

Sudden, unpredictable sleep during daily activities has occurred

Advise patients to avoid driving or operating machinery until effect is known

More common in Parkinson’s disease than in RLS

Augmentation in RLS

Symptoms may start earlier in the day or spread to other limbs

Occurs more frequently with long-term use or higher doses

Consider dose reduction, drug holiday, or alternative therapy

Hepatic and Renal Impairment

Use caution in hepatic dysfunction due to reduced clearance

Not recommended in severe renal impairment (CrCl <30 mL/min) without specialist supervision

Pregnancy and Lactation

Pregnancy

Animal studies show risk to fetus

No well-controlled human studies

Use only if benefits outweigh risks

Avoid in early pregnancy unless essential

Lactation

Not recommended

Suppresses prolactin and may interfere with lactation

Unknown if excreted in human milk

Pediatric Use

Safety and efficacy not established in children

Not approved for use in pediatric patients

Geriatric Use

Increased sensitivity possible

Slower titration and monitoring advised

Risk of hallucinations and hypotension is higher

Adverse Effects

Very Common

Nausea

Dizziness

Somnolence

Fatigue

Headache

Common

Vomiting

Orthostatic hypotension

Edema (peripheral)

Insomnia

Hallucinations

Constipation

Abdominal pain

Sweating

Confusion

Uncommon

Impulse control disorders

Syncope

Chest pain

Increased libido

Restlessness or agitation

Increased creatine kinase

Rare and Serious

Sudden sleep episodes

Neuroleptic malignant syndrome (after abrupt withdrawal)

Fibrotic complications (rare, mostly seen with ergot-derived agents)

Overdose

Symptoms

Agitation

Hallucinations

Vomiting

Tachycardia

Hypotension

Dyskinesia

Management

Supportive and symptomatic

Administer activated charcoal if within 1–2 hours of ingestion

Monitor cardiovascular and neurological status

Drug Interactions

CYP1A2 Inhibitors (e.g., ciprofloxacin, fluvoxamine)

Increase plasma concentration of ropinirole

May require dose reduction

Estrogens

May decrease clearance of ropinirole

Monitor clinical response in women on oral contraceptives or hormone replacement

CYP1A2 Inducers (e.g., smoking, omeprazole, carbamazepine)

Can reduce ropinirole levels

Dose adjustment may be necessary

Dopamine Antagonists (e.g., antipsychotics, metoclopramide)

Reduce efficacy of ropinirole

Avoid concomitant use

Alcohol and CNS depressants

Additive sedative effects

Increase risk of drowsiness and sudden sleep attacks

Levodopa

Synergistic effect in Parkinson's disease

May require levodopa dose reduction when adding ropinirole

Use in Special Populations

Renal impairment

Mild to moderate: no adjustment needed

Severe: use with caution; limited data

Hepatic impairment

Use cautiously due to reduced clearance

Monitor for adverse reactions

Monitoring Parameters

Assess therapeutic effect in PD (motor symptoms) and RLS (nighttime symptoms)

Monitor for signs of hypotension, hallucinations, and impulse control changes

Evaluate for augmentation in RLS patients

Routine LFTs not required unless clinically indicated

Periodic mental health assessment for psychiatric side effects

Assess sleep patterns and alertness

Comparative Pharmacology

Ropinirole vs Pramipexole

Both are non-ergot dopamine agonists

Pramipexole has longer half-life and greater renal clearance

Ropinirole is metabolized hepatically via CYP1A2

Ropinirole vs Levodopa

Levodopa is more effective in advanced PD

Ropinirole used earlier in disease or in combination with levodopa to reduce motor complications

Ropinirole vs Gabapentin (for RLS)

Gabapentin preferred in patients with comorbid pain or anxiety

Ropinirole more effective for classic RLS symptoms

Formulations Available

Immediate-release tablets: 0.25 mg, 0.5 mg, 1 mg, 2 mg, 3 mg, 4 mg, 5 mg

Extended-release tablets: 2 mg, 4 mg, 6 mg, 8 mg, 12 mg

ER formulation enables once-daily dosing for Parkinson’s disease

No ER formulation approved for RLS

Regulatory and Legal Status

Approved by FDA, EMA, MHRA, and other global health agencies

Prescription-only medication

Included in clinical guidelines for Parkinson’s disease and RLS