ROPINIRole (Lexi-Drugs)

Pronunciation

(roe PIN i role)

Brand Names: US

Requip XL; Requip [DSC]

Brand Names: Canada

ACT Ropinirole; JAMP-Ropinirole; PMS-Ropinirole; RAN-Ropinirole; Requip [DSC]

Dosing: Adult

Parkinson disease: Oral:

Immediate-release tablet: The dosage should be increased to achieve a maximum therapeutic effect, balanced against the principal side effects of nausea, dizziness, somnolence and dyskinesia. Recommended starting dose is 0.25 mg 3 times daily; based on individual patient response, the dosage should be titrated with weekly increments as described below:

• Week 1: 0.25 mg 3 times daily; total daily dose: 0.75 mg

• Week 2: 0.5 mg 3 times daily; total daily dose: 1.5 mg

• Week 3: 0.75 mg 3 times daily; total daily dose: 2.25 mg

• Week 4: 1 mg 3 times daily; total daily dose: 3 mg

Note: After week 4, if necessary, daily dosage may be increased by 1.5 mg/day on a weekly basis up to a dose of 9 mg/day, and then by up to 3 mg/day weekly to a total of 24 mg/day. If a significant interruption in therapy with ropinirole occurs, retitration may be warranted.

Parkinson disease discontinuation taper: Gradually taper over 7 days as follows: reduce frequency of administration from 3 times daily to twice daily for 4 days, then reduce to once daily for remaining 3 days.

Extended-release tablet: Initial: 2 mg once daily for 1 to 2 weeks, followed by increases of 2 mg/day at weekly or longer intervals based on therapeutic response and tolerability; there was no additional benefit shown for doses greater than 8 mg/day in advanced Parkinson disease or 12 mg/day in early Parkinson disease; maximum: 24 mg/day; Note: If a significant interruption in therapy with ropinirole occurs, retitration may be warranted. When discontinuing gradually taper over 7 days.

Restless legs syndrome (RLS): Oral: Immediate-release tablets: Initial: 0.25 mg once daily 1 to 3 hours before bedtime. Dose may be increased after 2 days to 0.5 mg daily, and after 7 days to 1 mg daily. Dose may be further titrated upward in 0.5 mg increments every week until reaching a daily dose of 3 mg during week 6. Daily dose may be increased to a maximum of 4 mg beginning week 7.

Note: If augmentation occurs, dose earlier in the day, divide into multiple daily doses, or consider switching to alternative therapy (Garcia-Borreguero 2016). If a significant interruption in therapy with ropinirole occurs, retitration may be warranted. Gradually taper dose if discontinuation is warranted.

Converting from ropinirole immediate-release tablets to ropinirole extended-release tablets: Choose a once daily extended-release dose that most closely matches current immediate-release daily dose.

Dosing: Geriatric

Titrate dose to clinical response. Refer to adult dosing.

Dosing: Renal Impairment: Adult

Moderate renal impairment (CrCl 30 to 50 mL/minute): No dosage adjustment necessary.

Severe renal impairment (CrCl <30 mL/minute): There are no dosage adjustments provided in the manufacturer’s labeling (has not been studied). Use with caution.

ESRD requiring hemodialysis:

Immediate release:

Parkinson disease: Initial: 0.25 mg 3 times daily; may titrate dose upward based on tolerability and efficacy (maximum dose: 18 mg/day); postdialysis supplemental doses are not required

Restless legs syndrome: Initial: 0.25 mg once daily; may titrate dose upward based on tolerability and efficacy (maximum dose: 3 mg/day); postdialysis supplemental doses are not required

Extended release: Initial: 2 mg once daily; may titrate dose upward based on tolerability and efficacy (maximum dose: 18 mg/day); postdialysis supplemental doses are not required

Dosing: Hepatic Impairment: Adult

There are no dosage adjustments provided in the manufacturer’s labeling (has not been studied). Titrate with caution.

Use: Labeled Indications

Parkinson disease: Treatment of Parkinson disease

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

Clinical Practice Guidelines

Parkinson Disease:

Canadian Neurological Sciences Federation, “Canadian Guidelines on Parkinson’s Disease,” 2012

Restless Legs Syndrome:

American Academy of Neurology, “Practice guideline summary: Treatment of restless legs syndrome in adults,” November 2016

American Academy of Sleep Medicine, “The treatment of restless legs syndrome and periodic limb movement disorder in adults – An update for 2012: Practice parameters with an evidence-based systematic review and meta-analysis,” 2012

European Federation of Neurological Societies, the European Neurological Society and the European Sleep Research Society, “European guidelines on management of restless legs syndrome: Report of a joint task force by the European Federation of Neurological Societies, the European Neurological Society and the European Sleep Research Society,” November 2012

International Restless Legs Syndrome Study Group (IRLSSG), European Restless Legs Syndrome Study Group (ERLSSG), and Restless Legs Syndrome Foundation, “Guidelines for the first-line treatment of restless legs syndrome/Willis-Ekbom disease, prevention and treatment of dopaminergic augmentation: A combined task force of the IRLSSG, ERLSSG and the RLS Foundation, “ May 2016

Administration: Oral

Administer without regard to meals. Swallow extended-release tablet whole; do not crush, divide, or chew.

Storage/Stability

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

Medication Patient Education with HCAHPS Considerations

• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)

•Patient may experience nausea, vomiting, constipation, diarrhea, fatigue, sweating a lot, abdominal pain, loss of strength and energy, rhinitis, pharyngitis, back pain, tremors, dry mouth, or joint pain. Have patient report immediately to prescriber signs of a urinary tract infection (hematuria, burning or painful urination, polyuria, fever, lower abdominal pain, or pelvic pain), severe dizziness, passing out, confusion, uncontrollable urges, skin growths, mole changes, severe headache, severe anxiety, vision changes, angina, tachycardia, abnormal heartbeat, bradycardia, hallucinations, mood changes, behavioral changes, shortness of breath, abnormal movements, swelling of arms or legs, burning or numbness feeling, memory impairment, difficulty focusing, muscle rigidity, or narcolepsy (HCAHPS).

• Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.

Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for health care professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience, and judgment in diagnosing, treating, and advising patients.

Medication Safety Issues
  Sound-alike/look-alike issues:
Contraindications

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

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 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, 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 one 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 pramipexole 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 blood pressure 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 restless leg syndrome (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.

Special populations:

• Elderly: May be prone to an increased risk of adverse drug reactions.

Dosage form specific issues:

• Extended release: Extended-release ropinirole is designed to release medication over a 24-hour period. If rapid gastrointestinal 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.

Geriatric Considerations

Since the dose is titrated to clinical response, no specific dosage adjustment is necessary in the elderly.

Pregnancy Considerations

Adverse events have been observed in animal reproduction studies. Information related to the use of ropinirole for the treatment of restless legs syndrome (RLS) 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).

Breast-Feeding Considerations

It is not known if ropinirole is present in breast milk. Ropinirole inhibits prolactin secretion in humans and may potentially inhibit lactation. According to the manufacturer, the decision to continue or discontinue breast-feeding during therapy should take into account the risk of infant exposure, the benefits of breast-feeding to the infant, and benefits of treatment to the mother.

Briggs’ Drugs in Pregnancy & Lactation
Adverse Reactions

Data inclusive of trials in early Parkinson disease (PD; without levodopa) and restless legs syndrome (RLS). Incidences reflect those in PD unless otherwise indicated.

>10%:

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

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

Gastrointestinal: Nausea (PD: 60%, extended release: 8% to 33%; RLS: 40%), vomiting (PD, RLS: 10% to 12%)

Infection: Viral infection (11%)

Neuromuscular & skeletal: Weakness (PD, RLS: 9% to 16%), back pain (PD, extended release: ≤15%)

1% to 10%:

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

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

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

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

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

Hepatic: Increased serum alkaline phosphatase (3%)

Infection: Influenza (RLS: 3%)

Neuromuscular & skeletal: Arthralgia (RLS: 4%), limb pain (RLS: 3%), muscle cramps (RLS: 3%), hyperkinesia (2%)

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

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

Miscellaneous: Fever

<1%, postmarketing, and/or case reports: Aggressive behavior, agitation, behavioral problems, delirium, delusion, disorientation, heart valve disease, impulse control disorder, interstitial pulmonary disease, mental status changes, paranoia, pleural effusion, pleuropulmonary fibrosis, psychiatric disturbance, psychosis

Metabolism/Transport Effects

Substrate of CYP1A2 (major), CYP3A4 (minor); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential

Drug Interactions 

Abiraterone Acetate: May increase the serum concentration of CYP1A2 Substrates (High risk with Inhibitors). Risk C: Monitor therapy

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

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

Alizapride: May diminish the therapeutic effect of Anti-Parkinson Agents (Dopamine Agonist). Risk X: 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. Risk D: Consider therapy modification

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

Antipsychotic Agents (First Generation [Typical]): May diminish the therapeutic effect of Anti-Parkinson Agents (Dopamine Agonist). Anti-Parkinson Agents (Dopamine Agonist) may diminish the therapeutic effect of Antipsychotic Agents (First Generation [Typical]). Management: Avoid concomitant therapy if possible and monitor for decreased effects of both agents when these combinations cannot be avoided. Atypical antipsychotics such as clozapine and quetiapine may be less likely to reduce the effects of anti-Parkinson agents.Risk D: Consider therapy modification

Antipsychotic Agents (Second Generation [Atypical]): May diminish the therapeutic effect of Anti-Parkinson Agents (Dopamine Agonist). Management: Consider using an alternative antipsychotic agent when possible in patients with Parkinson disease. If an atypical antipsychotic is necessary, consider using clozapine or quetiapine, which may convey the lowest interaction risk. Risk D: Consider therapy modification

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

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

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

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

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

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

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

Ciprofloxacin (Systemic): May increase the serum concentration of ROPINIRole. Risk C: Monitor therapy

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

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

CYP1A2 Inhibitors (Moderate): May decrease the metabolism of CYP1A2 Substrates (High risk with Inhibitors). Risk C: Monitor therapy

CYP1A2 Inhibitors (Strong): May decrease the metabolism of CYP1A2 Substrates (High risk with Inhibitors). Risk D: Consider therapy modification

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

Deferasirox: May increase the serum concentration of CYP1A2 Substrates (High risk with Inhibitors). Risk C: Monitor therapy

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Obeticholic Acid: May increase the serum concentration of CYP1A2 Substrates (High risk with Inhibitors). Risk C: 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. Risk D: Consider therapy modification

Peginterferon Alfa-2b: May increase the serum concentration of CYP1A2 Substrates (High risk with Inhibitors). Risk C: Monitor therapy

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

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

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

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

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

Solriamfetol: Anti-Parkinson Agents (Dopamine Agonist) may enhance the hypertensive effect of Solriamfetol. Risk C: Monitor therapy

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

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

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

Vemurafenib: May increase the serum concentration of CYP1A2 Substrates (High risk with Inhibitors). Management: Consider alternatives to such combinations whenever possible, particularly if the CYP1A2 substrate has a relatively narrow therapeutic index. Drugs listed as exceptions to this monograph are discussed in separate drug interaction monographs.Risk D: Consider therapy modification

Monitoring Parameters

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

Advanced Practitioners Physical Assessment/Monitoring

Monitor blood pressure periodically. Monitor for CNS depression/somnolence.

Nursing Physical Assessment/Monitoring

Monitor blood pressure periodically. Monitor for CNS depression/somnolence.

Dosage Forms: US

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

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

Dosage Forms: Canada

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

Tablet, Oral:

Requip: 0.25 mg [DSC] [contains POLYSORBATE 80]

Requip: 1 mg [DSC] [contains FD&C BLUE #2 ALUMINUM LAKE]

Requip: 2 mg [DSC]

Requip: 5 mg [DSC] [contains FD&C BLUE #2 ALUMINUM LAKE, POLYSORBATE 80]

Generic: 0.25 mg, 1 mg, 2 mg, 5 mg

Anatomic Therapeutic Chemical (ATC) Classification
  • N04BC04
Generic Available (US)

Yes

Pricing: US

Tablet, 24-hour (Requip XL Oral)

2 mg (per each): $5.91

4 mg (per each): $11.82

8 mg (per each): $17.72

Tablet, 24-hour (rOPINIRole HCl ER Oral)

2 mg (per each): $1.83 – $2.74

4 mg (per each): $3.67 – $5.47

6 mg (per each): $5.50 – $8.21

8 mg (per each): $5.50 – $8.21

12 mg (per each): $7.21 – $13.68

Tablets (Requip Oral)

5 mg (per each): $6.99

Tablets (rOPINIRole HCl Oral)

0.25 mg (per each): $0.57 – $2.52

0.5 mg (per each): $0.57 – $2.52

1 mg (per each): $0.57 – $2.52

2 mg (per each): $0.57 – $2.52

3 mg (per each): $0.67 – $2.62

4 mg (per each): $0.67 – $2.62

5 mg (per each): $0.67 – $2.62

Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer’s AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.

Mechanism of Action

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 D3than 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.

Pharmacodynamics/Kinetics

Absorption: Immediate release: Rapid

Distribution: Vd: 7.5 L/kg

Protein binding: 40%

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

Bioavailability: Absolute: 45% to 55%

Half-life elimination: ~6 hours

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

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

Pharmacodynamics/Kinetics: Additional Considerations

Renal function impairment: Clearance of ropinirole was reduced by ~30% in patients with ESRD on dialysis

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

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

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.

Local Anesthetic/Vasoconstrictor Precautions

No information available to require special precautions

Effects on Dental Treatment

Key adverse event(s) related to dental treatment: Xerostomia and dysphagia occur with use. Normal salivary flow resumes upon discontinuation of treatment.

Effects on Bleeding

No information available to require special precautions

Index Terms

Ropinirole HCl; Ropinirole Hydrochloride

FDA Approval Date
September 19, 1997
References

Aurora RN, Kristo DA, Bista SR, et al, “The Treatment of Restless Legs Syndrome and Periodic Limb Movement Disorder in Adults-An Update For 2012: Practice Parameters With an Evidence-Based Systematic Review and Meta-Analyses: An American Academy of Sleep Medicine Clinical Practice Guideline,” Sleep, 2012, 35(8):1039-62.[PubMed 22851801]

Dostal M, Weber-Schoendorfer C, Sobesky J, et al, “Pregnancy Outcome Following Use of Levodopa, Pramipexole, Ropinirole, and Rotigotine For Restless Legs Syndrome During Pregnancy: A Case Series,” Eur J Neurol, 2013, 20(9):1241-6.[PubMed 23083216]

Factor SA, “Current Status of Symptomatic Medical Therapy in Parkinson’s Disease,” Neurotherapeutics, 2008, 5(2):164-80.[PubMed 18394561]

Garcia-Borreguero D, Silber MH, Winkelman JW, et al. Guidelines for the first-line treatment of restless legs syndrome/Willis-Ekbom disease, prevention and treatment of dopaminergic augmentation: a combined task force of the IRLSSG, EURLSSG, and the RLS-foundation. Sleep Med. 2016;21:1-11. doi: 10.1016/j.sleep.2016.01.017.[PubMed 27448465]

Happe S, Sauter C, Klosch G, et al, “Gabapentin Versus Ropinirole in the Treatment of Idiopathic Restless Legs Syndrome,” Neuropsychobiology, 2003, 48(2):82-6.[PubMed 14504416]

Molina JA, Sàinz-Artiga MJ, Fraile A, et al, “Pathologic Gambling in Parkinson’s Disease: A Behavioral Manifestation of Pharmacologic Treatment,” Mov Disord, 2000, 15(5):869-72.[PubMed 11009192]

Olanow CW, Watts RL, and Koller WC, “An Algorithm (Decision Tree) for the Management of Parkinson’s Disease (2001): Treatment Guidelines,” Neurology, 2001, 56(11 Suppl 5):1-88.[PubMed 11402154]

Requip (ropinirole) [prescribing information]. Research Triangle Park, NC: GlaxoSmithKline; February 2018.

Requip XL (ropinirole) [prescribing information]. Research Triangle Park, NC: GlaxoSmithKline; February 2018.

Saletu M, Anderer P, Saletu-Zyhlarz GM, et al, “Comparative Placebo-Controlled Polysomnographic and Psychometric Studies on the Acute Effects of Gabapentin Versus Ropinirole in Restless Legs Syndrome,”J Neural Transm, 2010, 117(4):463-73.[PubMed 20049491]

Stern MB, “Contemporary Approaches to the Pharmacotherapeutic Management of Parkinson’s Disease: An Overview,” Neurology, 1997, 49(1 Suppl 1):2-9.[PubMed 9222162]

Watts RL, “The Role of Dopamine Agonists in Early Parkinson’s Disease,” Neurology, 1997, 49(1 Suppl 1):34-48.[PubMed 9222273]

Weintraub D, Siderowf AD, Potenza MN, et al, “Association of Dopamine Agonist Use With Impulse Control Disorders in Parkinson Disease,” Arch Neurol, 2006, 63(7):969-73.[PubMed 16831966]

Brand Names: International

Adartrel (CH, FR, GB, IE, NO, SE); Appese (AU); Dopapro (KR); Eminens (HR); Eppinix XL (GB); Newquip (KR); Pakinol (KR); Parkirop (IN); Perkirol (LK); Raponer PR (MT); Repinex XL (GB); Repreve (AU, NZ); Requip (AE, AR, AT, BB, BE, BG, CH, CL, CZ, DE, DK, EE, ES, FI, FR, GB, GR, HN, HR, HU, IE, IL, IT, JP, KW, LT, LU, LV, MT, MY, NL, NO, NZ, PK, PL, PT, RO, SA, SE, SG, SK, TR, TW); requip (SI); Requip CR (JP); Requip Depot (IS); Requip PD (HK, ID, KR, MY, PH, SG, TH, TW); Requip XL (BB, CY, ZW); Rolpryna (IE, LV); Ronirol (LK); Ropaccord (AU); Ropark (LK); Ropimax (KR)

Ropinirole (Patient Education – Adult Medication)
You must carefully read the “Consumer Information Use and Disclaimer” below in order to understand and correctly use this information
Pronunciation

(roe PIN i role)

Brand Names: US

Requip XL; Requip [DSC]

Brand Names: Canada

ACT-Ropinirole; JAMP-Ropinirole; PMS-Ropinirole; RAN-Ropinirole; Requip

What is this drug used for?
  • It is used to treat Parkinson’s disease.
  • It is used to treat restless leg syndrome.
What do I need to tell my doctor BEFORE I take this drug?
  • If you have an allergy to ropinirole or any other part of this drug.
  • If you are allergic to any drugs like this one, any other drugs, foods, or other substances. Tell your doctor about the allergy and what signs you had, like rash; hives; itching; shortness of breath; wheezing; cough; swelling of face, lips, tongue, or throat; or any other signs.
  • If you are taking another drug that has the same drug in it.
  • This drug may interact with other drugs or health problems.
  • Tell your doctor and pharmacist about all of your drugs (prescription or OTC, natural products, vitamins) and health problems. You must check to make sure that it is safe for you to take this drug with all of your drugs and health problems. Do not start, stop, or change the dose of any drug without checking with your doctor.
What are some things I need to know or do while I take this drug?
  • For all uses of this drug:
  • Tell all of your health care providers that you take this drug. This includes your doctors, nurses, pharmacists, and dentists.
  • Avoid driving and doing other tasks or actions that call for you to be alert until you see how this drug affects you.
  • To lower the chance of feeling dizzy or passing out, rise slowly if you have been sitting or lying down. Be careful going up and down stairs.
  • Do not stop taking this drug all of a sudden without calling your doctor. You may have a greater risk of side effects. If you need to stop this drug, you will want to slowly stop it as ordered by your doctor.
  • If you start or stop smoking, talk with your doctor. How much drug you take may need to be changed.
  • Talk with your doctor before you drink alcohol or use other drugs and natural products that slow your actions.
  • Check blood pressure and heart rate as the doctor has told you. Talk with the doctor.
  • Do not switch between different forms of this drug without first talking with the doctor.
  • If you are 65 or older, use this drug with care. You could have more side effects.
  • Tell your doctor if you are pregnant or plan on getting pregnant. You will need to talk about the benefits and risks of using this drug while you are pregnant.
  • Tell your doctor if you are breast-feeding. You will need to talk about any risks to your baby.
  • Parkinson’s disease:
  • The chance of a type of skin cancer called melanoma may be raised in people with Parkinson’s disease. It is not known if this drug may also raise the chance. Have skin exams while you take this drug. Talk with your doctor.
  • Restless leg syndrome:
  • Tell your doctor if your signs become worse or start earlier in the day.
  • Have your skin checked as you have been told by your doctor. Talk with your doctor.
What are some side effects that I need to call my doctor about right away?
  • 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:
  • 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.
  • Signs of high or low blood pressure like very bad headache or dizziness, passing out, or change in eyesight.
  • Signs of a urinary tract infection (UTI) like blood in the urine, burning or pain when passing urine, feeling the need to pass urine often or right away, fever, lower stomach pain, or pelvic pain.
  • Feeling confused.
  • Strong urges that are hard to control (such as eating, gambling, sex, or spending money).
  • A skin lump or growth.
  • Change in color or size of a mole.
  • Very nervous and excitable.
  • Change in eyesight.
  • Chest pain or pressure or a fast heartbeat.
  • A heartbeat that does not feel normal.
  • Slow heartbeat.
  • Hallucinations (seeing or hearing things that are not there).
  • Mood changes.
  • Change in how you act.
  • Shortness of breath.
  • Trouble controlling body movements that is new or worse.
  • Swelling in the arms or legs.
  • A burning, numbness, or tingling feeling that is not normal.
  • Memory problems or loss.
  • Not able to focus.
  • Fever.
  • Muscle stiffness.
  • Some people have fallen asleep during activities like driving, eating, or talking. Some people did not feel sleepy and felt alert right before falling asleep. This has happened up to 1 year after this drug was started. If you fall asleep during activities, do not drive or do other tasks or actions that call for you to be alert while you take this drug. Call your doctor right away if this happens or you feel very sleepy.
What are some other side effects of this drug?
  • 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:
  • Upset stomach or throwing up.
  • Dizziness.
  • Constipation.
  • Diarrhea.
  • Feeling sleepy.
  • Headache.
  • Sweating a lot.
  • Belly pain.
  • Feeling tired or weak.
  • Dry mouth.
  • Joint pain.
  • Feeling nervous and excitable.
  • Shakiness.
  • Anxiety.
  • Nose or throat irritation.
  • Back pain.
  • These are not all of the side effects that may occur. If you have questions about side effects, call your doctor. Call your doctor for medical advice about side effects.
  • You may report side effects to your national health agency.
How is this drug best taken?
  • Use this drug as ordered by your doctor. Read all information given to you. Follow all instructions closely.
  • All products:
  • Take with or without food.
  • To gain the most benefit, do not miss doses.
  • Keep taking this drug as you have been told by your doctor or other health care provider, even if you feel well.
  • If you stop taking this drug, talk with your doctor. You may need to be restarted at a lower dose and raise the dose slowly.
  • Tablets:
  • For restless leg syndrome, take this drug 1 to 3 hours before bedtime.
  • Extended-release tablets:
  • Swallow whole. Do not chew, break, or crush.
  • If you have a health problem like diarrhea where this drug goes through the body too quickly, you may see something that looks like the tablet in your stool. If this happens, talk with your doctor.
What do I do if I miss a dose?
  • Take a missed dose as soon as you think about it.
  • If it is close to the time for your next dose, skip the missed dose and go back to your normal time.
  • Do not take 2 doses at the same time or extra doses.
  • If you miss a few days of this drug, call your doctor to find out how to restart.
How do I store and/or throw out this drug?
  • Store at room temperature.
  • Protect from light.
  • Keep lid tightly closed.
  • Store in a dry place. Do not store in a bathroom.
  • Keep all drugs in a safe place. Keep all drugs out of the reach of children and pets.
  • Throw away unused or expired drugs. Do not flush down a toilet or pour down a drain unless you are told to do so. Check with your pharmacist if you have questions about the best way to throw out drugs. There may be drug take-back programs in your area.
General drug facts
  • If your symptoms or health problems do not get better or if they become worse, call your doctor.
  • Do not share your drugs with others and do not take anyone else’s drugs.
  • Keep a list of all your drugs (prescription, natural products, vitamins, OTC) with you. Give this list to your doctor.
  • Talk with the doctor before starting any new drug, including prescription or OTC, natural products, or vitamins.
  • Some drugs may have another patient information leaflet. If you have any questions about this drug, please talk with your doctor, nurse, pharmacist, or other health care provider.
  • If you think there has been an overdose, call your poison control center or get medical care right away. Be ready to tell or show what was taken, how much, and when it happened.