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ROPINIRole

Medically reviewed by Drugs.com. Last updated on May 4, 2020.

Pronunciation

(roe PIN i role)

Index Terms

  • Ropinirole HCl
  • Ropinirole Hydrochloride

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product

Tablet, Oral:

Requip: 0.25 mg [DSC], 0.5 mg [DSC], 1 mg [DSC], 2 mg [DSC], 3 mg [DSC], 4 mg [DSC], 5 mg [DSC] [contains fd&c blue #2 aluminum lake, fd&c yellow #6 aluminum lake, polysorbate 80]

Generic: 0.25 mg, 0.5 mg, 1 mg, 2 mg, 3 mg, 4 mg, 5 mg

Tablet Extended Release 24 Hour, Oral:

Requip XL: 2 mg [DSC], 4 mg [DSC], 6 mg, 8 mg [DSC], 12 mg [contains fd&c blue #2 aluminum lake, fd&c yellow #6 aluminum lake]

Generic: 2 mg, 4 mg, 6 mg, 8 mg, 12 mg

Brand Names: U.S.

  • Requip XL
  • Requip [DSC]

Pharmacologic Category

  • Anti-Parkinson Agent, Dopamine Agonist

Pharmacology

Ropinirole has a high relative in vitro specificity and full intrinsic activity at the D2 and D3 dopamine receptor subtypes, binding with higher affinity to D3 than to D2 or D4 receptor subtypes; relevance of D3 receptor binding in Parkinson disease is unknown. Ropinirole has moderate in vitro affinity for opioid receptors. Ropinirole and its metabolites have negligible in vitro affinity for dopamine D1, 5-HT1, 5-HT2, benzodiazepine, GABA, muscarinic, alpha1-, alpha2-, and beta-adrenoreceptors. Although precise mechanism of action of ropinirole is unknown, it is believed to be due to stimulation of postsynaptic dopamine D2-type receptors within the caudate putamen in the brain. Ropinirole caused decreases in systolic and diastolic blood pressure at doses >0.25 mg. The mechanism of ropinirole-induced postural hypotension is believed to be due to D2-mediated blunting of the noradrenergic response to standing and subsequent decrease in peripheral vascular resistance.

Absorption

Immediate release: Rapid

Distribution

Vd: 7.5 L/kg

Metabolism

Extensively hepatic via CYP1A2 to inactive metabolites; first-pass effect

Excretion

Urine (<10% as unchanged drug, 60% as metabolites)

Time to Peak

Immediate release: ~1-2 hours; Extended release: 6-10 hours; Tmax increased by 2.5-3 hours when taken with a high-fat meal

Half-Life Elimination

~6 hours

Protein Binding

40%

Special Populations: Renal Function Impairment

Clearance of ropinirole was reduced by ~30% in patients with ESRD on dialysis

Special Populations: Hepatic Function Impairment

Patients with hepatic impairment may have higher plasma levels and lower clearance of ropinirole

Special Populations: Elderly

Oral clearance is reduced ~15% in patients >65 years

Special Populations Note

Cigarette smoking: Clearance is expected to increase because CYP1A2 is known to be induced by smoking. Cmax was 30% and AUC was 38% lower in smokers compared with nonsmokers.

Use: Labeled Indications

Parkinson disease: Treatment of Parkinson disease.

Restless legs syndrome (immediate release only): Treatment of moderate to severe primary restless legs syndrome.

Contraindications

Hypersensitivity (eg, urticaria, angioedema, rash, pruritus) to ropinirole or any component of the formulation

Dosing: Adult

Parkinson disease (monotherapy or adjunctive therapy):

Immediate release: Oral:

Initial: 0.25 mg 3 times daily; may increase daily dose based on response and tolerability. For doses up to 3 mg/day, may increase daily dose by 0.75 mg every 7 days; for doses from 3 to 9 mg/day, may increase daily dose by 1.5 mg every 7 days; for doses >9 mg/day, may increase daily dose by 3 mg every 7 days.

Maximum dose: 24 mg/day in 3 divided doses (Spindler 2020; manufacturer's labeling).

Usual dose: 12 to 16 mg/day (Spindler 2020).

Extended release: Oral:

Initial: 2 mg once daily for 1 to 2 weeks; may increase daily dose by 2 mg at weekly or longer intervals based on response and tolerability.

Maximum dose: 24 mg/day (Pahwa 2007; Stocchi 2008; manufacturer's labeling).

Usual dose: 12 to 16 mg/day (Spindler 2020).

Converting from ropinirole immediate release to ropinirole extended release: May initiate extended release the morning after the last immediate release evening dose is taken. The total daily dose should remain the same.

Restless legs syndrome (monotherapy or adjunctive therapy):

Immediate release: Oral:

Initial: 0.25 mg once daily 1 to 3 hours before bedtime. Dose may be increased after 2 days to 0.5 mg once daily, and after 7 days to 1 mg once daily. Dose may be further increased in 0.5 mg increments every week until reaching 3 mg once daily during week 6. Dose may be increased to a maximum of 4 mg once daily beginning week 7 (manufacturer's labeling). Alternatively, some experts increase by 0.25 mg every 2 to 3 days based on response and tolerability to lowest effective dose, up to a maximum of 4 mg once daily (Silber 2020).

Note: If augmentation occurs, dose earlier in the day, divide into multiple daily doses, or consider switching to alternative therapy (Garcia-Borreguero 2016).

Discontinuation of therapy: Do not discontinue abruptly; gradually taper over 7 days. For IR formulation, some patients may tolerate a reduction in frequency of administration from 3 times daily to twice daily for 4 days, then once daily for the remaining 3 days.

Dosing: Geriatric

Refer to adult dosing.

Administration

Oral: Administer without regard to meals. Swallow ER tablet whole; do not crush, divide, or chew.

Bariatric surgery: Tablet, extended release: Some institutions may have specific protocols that conflict with these recommendations; refer to institutional protocols as appropriate. IR formulation is available. If safety and efficacy can be effectively monitored, no change in formulation or administration is required after bariatric surgery.

Storage

Store at 68°F to 77°F (20°C to 25°C). Protect from light.

Drug Interactions

Abametapir: May increase the serum concentration of CYP1A2 Substrates (High risk with Inhibitors). Avoid combination

Alcohol (Ethyl): May enhance the sedative effect of ROPINIRole. Monitor therapy

Alfuzosin: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Alizapride: May diminish the therapeutic effect of Anti-Parkinson Agents (Dopamine Agonist). Avoid combination

Amifostine: Blood Pressure Lowering Agents may enhance the hypotensive effect of Amifostine. Management: When amifostine is used at chemotherapy doses, blood pressure lowering medications should be withheld for 24 hours prior to amifostine administration. If blood pressure lowering therapy cannot be withheld, amifostine should not be administered. Consider therapy modification

Amisulpride (Injection): May diminish the therapeutic effect of Anti-Parkinson Agents (Dopamine Agonist). Avoid combination

Amisulpride (Oral): Anti-Parkinson Agents (Dopamine Agonist) may diminish the therapeutic effect of Amisulpride (Oral). Amisulpride (Oral) may diminish the therapeutic effect of Anti-Parkinson Agents (Dopamine Agonist). Avoid combination

Antipsychotic Agents (First Generation [Typical]): Anti-Parkinson Agents (Dopamine Agonist) may diminish the therapeutic effect of Antipsychotic Agents (First Generation [Typical]). Antipsychotic Agents (First Generation [Typical]) may diminish the therapeutic effect of Anti-Parkinson Agents (Dopamine Agonist). Management: Avoid concomitant therapy if possible. If antipsychotic use is necessary, consider using atypical antipsychotics such as clozapine, quetiapine, or ziprasidone at lower initial doses, or a non-dopamine antagonist (eg, pimavanserin). Exceptions: Methotrimeprazine. Consider therapy modification

Antipsychotic Agents (Second Generation [Atypical]): May diminish the therapeutic effect of Anti-Parkinson Agents (Dopamine Agonist). Management: Consider avoiding atypical antipsychotic use in patients with Parkinson disease. If an atypical antipsychotic is necessary, consider using clozapine, quetiapine, or ziprasidone at lower initial doses, or a non-dopamine antagonist (eg, pimavanserin). Consider therapy modification

Blood Pressure Lowering Agents: May enhance the hypotensive effect of Hypotension-Associated Agents. Monitor therapy

Brimonidine (Topical): May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Brivudine [INT]: May enhance the adverse/toxic effect of Anti-Parkinson Agents (Dopamine Agonist). Specifically, the risk of chorea may be increased. Monitor therapy

Broccoli: May decrease the serum concentration of CYP1A2 Substrates (High risk with Inducers). Monitor therapy

Bromopride: May diminish the therapeutic effect of Anti-Parkinson Agents (Dopamine Agonist). Monitor therapy

Bromperidol: May diminish the hypotensive effect of Blood Pressure Lowering Agents. Blood Pressure Lowering Agents may enhance the hypotensive effect of Bromperidol. Avoid combination

BuPROPion: Anti-Parkinson Agents (Dopamine Agonist) may enhance the adverse/toxic effect of BuPROPion. Monitor therapy

Cannabis: May decrease the serum concentration of CYP1A2 Substrates (High risk with Inducers). Monitor therapy

CNS Depressants: May enhance the sedative effect of ROPINIRole. Monitor therapy

CYP1A2 Inducers (Moderate): May decrease the serum concentration of ROPINIRole. Monitor therapy

CYP1A2 Inhibitors (Moderate): May increase the serum concentration of ROPINIRole. Monitor therapy

CYP1A2 Inhibitors (Strong): May increase the serum concentration of ROPINIRole. Monitor therapy

Diazoxide: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

DULoxetine: Blood Pressure Lowering Agents may enhance the hypotensive effect of DULoxetine. Monitor therapy

Estrogen Derivatives: May increase the serum concentration of ROPINIRole. Monitor therapy

Herbs (Hypotensive Properties): May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Hypotension-Associated Agents: Blood Pressure Lowering Agents may enhance the hypotensive effect of Hypotension-Associated Agents. Monitor therapy

Levodopa-Containing Products: Blood Pressure Lowering Agents may enhance the hypotensive effect of Levodopa-Containing Products. Monitor therapy

Lormetazepam: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Methotrimeprazine: Anti-Parkinson Agents (Dopamine Agonist) may diminish the therapeutic effect of Methotrimeprazine. Methotrimeprazine may diminish the therapeutic effect of Anti-Parkinson Agents (Dopamine Agonist). Avoid combination

Methylphenidate: May enhance the adverse/toxic effect of Anti-Parkinson Agents (Dopamine Agonist). Monitor therapy

Metoclopramide: May diminish the therapeutic effect of Anti-Parkinson Agents (Dopamine Agonist). Avoid combination

Molsidomine: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Naftopidil: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Nicergoline: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Nicorandil: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Nitroprusside: Blood Pressure Lowering Agents may enhance the hypotensive effect of Nitroprusside. Monitor therapy

Obinutuzumab: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Management: Consider temporarily withholding blood pressure lowering medications beginning 12 hours prior to obinutuzumab infusion and continuing until 1 hour after the end of the infusion. Consider therapy modification

Pentoxifylline: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Pholcodine: Blood Pressure Lowering Agents may enhance the hypotensive effect of Pholcodine. Monitor therapy

Phosphodiesterase 5 Inhibitors: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Prostacyclin Analogues: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Quinagolide: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Solriamfetol: May enhance the adverse/toxic effect of Anti-Parkinson Agents (Dopamine Agonist). Monitor therapy

Sulpiride: May diminish the therapeutic effect of Anti-Parkinson Agents (Dopamine Agonist). Avoid combination

Tobacco (Smoked): May decrease the serum concentration of ROPINIRole. Monitor therapy

Adverse Reactions

Data inclusive of trials in early Parkinson disease (PD) without levodopa and restless legs syndrome (RLS). Extended-release data from trials in early PD without levodopa. As reported with immediate-release formulation, unless otherwise noted.

>10%:

Cardiovascular: Hypotension (RLS: ≤25%; PD: 2%), orthostatic hypotension (RLS: ≤25%; PD: 6%; extended release: 14%), hypertension (PD: 5%; extended release: 3% to 15%), syncope (PD: ≤12%; RLS: 1% to 2%; sometimes associated with bradycardia)

Central nervous system: Drowsiness (PD: ≤40%; extended release: 8% to 15%; RLS: 12%), dizziness (PD: 40%; extended release: 6% to 10%; RLS: 11%), headache (PD, extended release: 5% to 15%)

Gastrointestinal: Nausea (PD: 60%; RLS: 40%; extended release: 10% to 33%), vomiting (PD: 12%; extended release: 10%; RLS: 11%)

Infection: Viral infection (PD: 11%)

Neuromuscular & skeletal: Asthenia (PD: 16%; RLS: 9%), back pain (PD, extended release: 5% to 15%)

1% to 10%:

Cardiovascular: Lower extremity edema (PD: 7%), dependent edema (PD: 6%), chest pain (PD: 4%), flushing (PD: 3%), palpitations (PD: 3%), peripheral ischemia (PD: 3%), atrial fibrillation (PD: 2%), extrasystoles (PD: 2%), peripheral edema (RLS: 2%), tachycardia (PD: 2%)

Central nervous system: Pain (PD: 8%), confusion (PD: 5%), hallucination (PD: 5%), narcolepsy (PD, extended release: 5% to 10%), hypoesthesia (PD: 4%), amnesia (PD: 3%), paresthesia (RLS: 3%), yawning (PD: 3%), lack of concentration (PD: 2%), vertigo (2%)

Dermatologic: Diaphoresis (PD: 6%), hyperhidrosis (RLS: 3%)

Gastrointestinal: Dyspepsia (PD: 10%; RLS: 4%), abdominal pain (PD: 6% to 7%; includes immediate release and extended release), constipation (PD, extended release: 5%), diarrhea (RLS: 5%), xerostomia (PD: 5%; RLS: 3%), anorexia (PD: 4%), flatulence (PD: 3%), upper abdominal pain (RLS: 3%)

Genitourinary: Urinary tract infection (PD: 5%), impotence (PD: 3%)

Hepatic: Increased serum alkaline phosphatase (PD: 3%)

Infection: Influenza (RLS: 3%)

Neuromuscular & skeletal: Increased creatine phosphokinase in blood specimen (PD, extended release: 10%), arthralgia (RLS: 4%), limb pain (RLS: 3%), muscle cramps (RLS: 3%), hyperkinetic muscle activity (PD: 2%)

Ophthalmic: Visual disturbance (PD: 6%), eye disease (PD: 3%), xerophthalmia (PD: 2%)

Respiratory: Nasopharyngitis (RLS: 9%), pharyngitis (PD: 6%), rhinitis (PD: 4%), sinusitis (PD: 4%), bronchitis (PD: 3%), cough (RLS: 3%), dyspnea (PD: 3%), nasal congestion (RLS: 2%)

<1%: Pleural effusion

Postmarketing: Aggressive behavior, agitation, behavioral problems, delirium, delusion, disorientation, heart valve disease, impulse control disorder (Bastiaens 2013; Corvol 2018), interstitial pulmonary disease, mental status changes, paranoid ideation, pleuropulmonary fibrosis, psychiatric disturbance, psychosis

Warnings/Precautions

Concerns related to adverse effects:

• Dyskinesias: May cause and/or exacerbate dyskinesias. Use with caution in patients with preexisting dyskinesias. Decreasing the dose may alleviate this condition.

• Impulse control disorders: Has been associated with compulsive behaviors and/or loss of impulse control, which has manifested as pathological gambling, libido increases (hypersexuality), compulsive buying, binge or compulsive eating, and/or other intense urges. Dose reduction or discontinuation of therapy has been reported to reverse these behaviors in some, but not all cases.

• Melanoma: Risk for melanoma development is increased in Parkinson disease patients; drug causation or factors contributing to risk have not been established. Patients should be monitored closely and periodic skin examinations should be performed.

• Orthostatic hypotension: May cause orthostatic hypotension; Parkinson disease patients appear to have an impaired capacity to respond to a postural challenge. Use with caution in patients at risk of hypotension (such as those receiving antihypertensive or antiarrhythmic drugs) or where transient hypotensive episodes would be poorly tolerated (cardiovascular disease or cerebrovascular disease). Parkinson patients being treated with dopaminergic agonists ordinarily require careful monitoring for signs and symptoms of postural hypotension, especially during dose escalation, and should be informed of this risk. Syncope, sometimes associated with bradycardia, was observed in association with ropinirole in early Parkinson disease patients and patients with restless leg syndrome (RLS).

• Pleural/retroperitoneal fibrosis: Ergot-derived dopamine agonists have been associated with fibrotic complications (eg, pericarditis, retroperitoneal fibrosis, pleural effusion, pleural thickening, pulmonary infiltrates, cardiac valvulopathy). Although ropinirole is not an ergot, there have been postmarketing reports of possible fibrotic complications (pleural effusion, pleural fibrosis, interstitial lung disease, and cardiac valvulopathy) with ropinirole; monitor closely for signs and symptoms of fibrosis. Discontinuation of therapy may resolve complications, but not in all cases.

• Psychotic effects: May cause hallucinations, particularly in older patients. May also cause or exacerbate mental status and behavioral changes, which may be severe, including psychotic-like behavior during treatment or after starting or increasing the dose; manifestations may include paranoid ideation, delusions, hallucinations, confusion, psychotic-like behavior, mania, disorientation, aggressive behavior, agitation, and delirium. Avoid use in patients with a major psychotic disorder.

• Retinal changes: Pathologic degenerative changes were observed in the retinas of albino rats during studies with this agent, but were not observed in the retinas of albino mice or in other species. The significance of these data for humans remains uncertain.

• Somnolence: Patients have reported falling asleep while engaging in activities of daily living; this has been reported to occur without significant warning signs; some of these events had been reported 1 year after the initiation of therapy. Ropinirole has also been associated with somnolence. Before initiating treatment, advise patients of the potential to develop drowsiness, and inquire about factors that may increase the risk (eg, concomitant sedating medications and/or alcohol, presence of sleep disorders, concomitant medications that increase ropinirole plasma levels). Patients must be cautioned about performing tasks which require mental alertness (eg, operating machinery or driving). Monitor for daytime somnolence or preexisting sleep disorder; discontinue if significant daytime sleepiness or episodes of falling asleep occur; if a decision is made to continue therapy, advise patients not to drive and to avoid other potentially dangerous activities.

Disease-related concerns:

• Cardiovascular disease: Use with caution in patients with cardiovascular disease because of a risk for elevation in BP and changes in heart rate.

• Hepatic impairment: Use with caution in patients with hepatic impairment (extensively metabolized).

• Renal impairment: Dosage adjustment recommended in patients with ESRD on dialysis.

• Restless legs syndrome: Augmentation (earlier onset of symptoms in the evening/afternoon, increase and/or spread of symptoms to other extremities) may occur in some RLS patients. Risk factors for dopaminergic-induced augmentation include higher doses of dopaminergic agents, use of shorter-acting dopamine agonists (ie, pramipexole, ropinirole) or levodopa, low iron stores, and increased severity of symptoms prior to treatment initiation. To minimize risk of augmentation, treatment should only be initiated when symptoms significantly impact quality of life; intermittent treatment should also be considered. If dopaminergic agents are used as initial treatment, use the lowest effective dose and avoid exceeding recommended doses. If augmentation occurs, dose earlier in the day, divide into multiple daily doses, or consider switching to alternative therapy (Garcia-Borreguero 2016). End-of-dose rebound (reappearance of symptoms in the early morning hours) may also occur. Consider dosage adjustment or discontinuation of treatment if rebound symptoms occur.

Concurrent drug therapy issues:

• Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.

Dosage form specific issues:

• Extended release: ER ropinirole is designed to release medication over a 24-hour period. If rapid GI transit occurs, there may be risk of incomplete release of medication and medication residue being passed in the stool.

Other warnings/precautions:

• Discontinuation of therapy: Taper gradually when discontinuing therapy; dopaminergic agents have been associated with a syndrome resembling neuroleptic malignant syndrome on abrupt withdrawal or significant dosage reduction after long-term use.

Monitoring Parameters

Blood pressure (orthostatic); daytime alertness; CNS depression, fall risk, behavior changes (eg, compulsive behaviors); periodic skin examinations

Pregnancy Considerations

Information related to the use of ropinirole for the treatment of restless legs syndrome in pregnant women is limited. Current guidelines note that the available information is insufficient to make a recommendation for use in pregnant women (Aurora 2012; Dostal 2013; Tüfekçioğlu 2018).

Patient Education

What is this drug used for?

• It is used to treat Parkinson's disease.

• It is used to treat restless leg syndrome.

All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your doctor or get medical help if any of these side effects or any other side effects bother you or do not go away:

• Nausea

• Vomiting

• Constipation

• Diarrhea

• Fatigue

• Sweating a lot

• Abdominal pain

• Loss of strength and energy

• Nose irritation

• Throat irritation

• Back pain

• Tremors

• Dry mouth

• Joint pain

• Anxiety

WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:

• Urinary tract infection like blood in the urine, burning or painful urination, passing a lot of urine, fever, lower abdominal pain, or pelvic pain

• Severe dizziness

• Passing out

• Confusion

• Uncontrollable urges

• Skin lump or growth

• Mole changes

• Severe headache

• Vision changes

• Chest pain

• Fast heartbeat

• Abnormal heartbeat

• Slow heartbeat

• Sensing things that seem real but are not

• Mood changes

• Behavioral changes

• Shortness of breath

• Abnormal movements

• Swelling

• Burning or numbness feeling

• Trouble with memory

• Trouble focusing

• Stiff muscles

• Narcolepsy

• Severe fatigue

• Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing, swallowing, or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.

Note: This is not a comprehensive list of all side effects. Talk to your doctor if you have questions.

Consumer Information Use and Disclaimer: This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a limited summary of general information about the medicine's uses from the patient education leaflet and is not intended to be comprehensive. This limited summary does NOT include all information available about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not intended to provide medical advice, diagnosis or treatment and does not replace information you receive from the healthcare provider. For a more detailed summary of information about the risks and benefits of using this medicine, please speak with your healthcare provider and review the entire patient education leaflet.

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.