Ropinirole: Drug information

(For additional information see "Ropinirole: Patient drug information")

For abbreviations, symbols, and age group definitions used in Lexicomp (show table)

Brand Names: US

Requip XL [DSC];
Requip [DSC]

Brand Names: Canada

JAMP-Ropinirole;
PMS-Ropinirole;
RAN-Ropinirole;
TEVA-Ropinirole

Pharmacologic Category

Anti-Parkinson Agent, Dopamine Agonist

Dosing: Adult

Parkinson disease

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 (Ref).

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

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 (Ref).

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

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

Restless legs syndrome (alternative agent):

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/day beginning week 7 (Ref). Alternatively, some experts recommend increasing 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/day (Ref).

Note: If augmentation occurs (worsening symptoms during dopaminergic therapy), dose earlier in the evening, divide into multiple evening doses, increase dose (keeping at or below 4 mg/day), or consider switching to alternative therapy (Ref).

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.

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Dosing: Kidney Impairment: Adult

The renal dosing recommendations are based upon the best available evidence and clinical expertise. Senior Editorial Team: Bruce Mueller, PharmD, FCCP, FASN, FNKF; Jason Roberts, PhD, BPharm (Hons), B App Sc, FSHP, FISAC; Michael Heung, MD, MS.

Altered kidney function:

CrCl ≥30 mL/minute: No dosage adjustment necessary (Ref).

CrCl <30 mL/minute: There are no dosage adjustments provided in the manufacturer's labeling (has not been studied); however, the following doses are recommended (based on pharmacokinetic data in patients on hemodialysis):

Restless legs syndrome:

Immediate release: Initial: 0.25 mg once daily; may titrate dose upward gradually based on tolerability and response at intervals greater than or equal to those recommended for patients with normal kidney function (maximum dose: 3 mg/day) (Ref).

Parkinson disease:

Immediate release: Initial: 0.25 mg 3 times daily; may titrate dose upward gradually based on tolerability and response at intervals greater than or equal to those recommended for patients with normal kidney function (maximum dose: 18 mg/day in 3 divided doses) (Ref).

Extended release: Initial: 2 mg once daily; may titrate dose upward gradually based on tolerability and response at intervals greater than or equal to those recommended for patients with normal kidney function (maximum dose: 18 mg/day) (Ref).

Hemodialysis, intermittent (thrice weekly): Unlikely to be significantly removed by hemodialysis (large V_d) (Ref):

Restless legs syndrome:

Immediate release: Initial: 0.25 mg once daily; may titrate dose upward gradually based on tolerability and response at intervals ≥ to those recommended for patients with normal kidney function (maximum dose: 3 mg/day) (Ref); studies in this population utilized ≤2 mg/day (Ref). Postdialysis supplemental doses are not required (Ref).

Parkinson disease:

Immediate release: Initial: 0.25 mg 3 times daily; may titrate dose upward based on tolerability and response (maximum dose: 18 mg/day in 3 divided doses); postdialysis supplemental doses are not required (Ref).

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

Peritoneal dialysis: Unlikely to be significantly removed by peritoneal dialysis (large V_d) (Ref):

Restless legs syndrome:

Immediate release : Initial: 0.25 mg once daily; may titrate dose upward gradually based on tolerability and response at intervals greater than or equal to those recommended for patients with normal kidney function (maximum dose: 3 mg/day) (Ref).

Parkinson disease:

Immediate release: Initial: 0.25 mg 3 times daily; may titrate dose upward based on tolerability and response (maximum dose: 18 mg/day in 3 divided doses) (Ref).

Extended release: Initial: 2 mg once daily; may titrate dose upward based on tolerability and response at intervals greater than or equal to those recommended for patients with normal kidney function (maximum dose: 18 mg/day) (Ref).

CRRT: Unlikely to be significantly removed by CRRT (large V_d). Dose as if the patient has a CrCl <30 mL/minute (Ref).

PIRRT (eg, sustained, low-efficiency diafiltration): Unlikely to be significantly removed by PIRRT (large V_d). Dose as if the patient has a CrCl <30 mL/minute (Ref).

Dosing: Hepatic Impairment: Adult

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

Dosing: Older Adult

Refer to adult dosing.

Dosage Forms: US

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

Tablet, Oral:

Requip: 1 mg [DSC], 4 mg [DSC], 5 mg [DSC] [contains fd&c blue #2 (indigo carm) aluminum lake, fd&c yellow #6(sunset yellow)alumin 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 [DSC], 8 mg [DSC], 12 mg [DSC] [contains fd&c blue #2 (indigo carm) aluminum lake, fd&c yellow #6(sunset yellow)alumin lake]

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

Generic Equivalent Available: US

Yes

Dosage Forms: Canada

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Tablet, Oral:

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

Administration: Adult

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.

Use: Labeled Indications

Parkinson disease: Treatment of Parkinson disease.

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

Medication Safety Issues

Sound-alike/look-alike issues:

Requip may be confused with Reglan.

ROPINIRole may be confused with RisperDAL, risperiDONE, ropivacaine.

Adverse Reactions (Significant): Considerations

Augmentation

Augmentation, a worsening of symptoms beyond the level of severity that was experienced when the medication was initiated, has been reported with dopamine agonists such as ropinirole, in patients with restless leg syndrome (RLS) (Ref). In addition to severity, the symptoms occur at an earlier time of day compared to pretreatment timing of symptoms (Ref). A pooled meta-analysis reported an overall augmentation rate of 5.6% in RLS with treatment (not specifically with ropinirole) (Ref). Historically, treatment with levodopa has been associated with the highest rate followed by dopamine agonists, such as ropinirole (Ref). In one study with ropinirole alone, augmentation occurred in up to 4% and was clinically meaningful in most cases (Ref).

Mechanism: Dose- and duration-related; not clearly established. Proposed mechanisms include increased dopamine concentrations in the CNS and overstimulation of the dopamine D₁ receptors compared to dopamine D₂ receptors in the spinal cord (Ref). Iron deficiency may also reduce the function of the dopamine transporter, increasing dopamine concentrations (Ref). In addition, augmentation may also result from dopamine receptor down-regulation, which lowers tolerance to dopaminergic effects in a circadian manner (Ref).

Onset: Delayed; usually after months of treatment (mean duration 8.8 months in one study with pramipexole) (Ref).

Risk factors:

• Higher doses (Ref)

• Longer duration of therapy (Ref)

• More severe RLS prior to treatment (may be related to higher dose use) (Ref)

• Iron deficiency (Ref)

• Older patients (Ref)

• Use of IR formulations (Ref)

Impulse control and related disorders

Ropinirole has been associated with impulse control disorders and related disorders, manifesting as pathological gambling, increased libido (hypersexuality), compulsive or binge buying/eating, and/or other intense urges. The prevalence of impulsive control was reported to range from 2.6% to 34.8% in Parkinson disease (PD). A lower prevalence was reported in patients taking dopamine agonists, such as ropinirole, for restless leg syndrome (RLS) (Ref). Dose reduction or discontinuation of therapy has been reported to reverse these behaviors in some, but not all cases.

Mechanism: Possibly dose-related; may be due to activation of dopamine receptors (mostly D₃) involved in both the nigrostriatal and the reward pathways (Ref).

Onset: Difficult to determine. In one study, the incidence of impulsive behavior was relatively low during the first 30 months of exposure but higher over the next 30 months (Ref).

Risk factors:

• Higher doses (Ref)

• Higher affinity for D₃ receptors (Ref)

• Males (for PD) (Ref)

• Younger age (Ref)

• History of psychiatric symptoms (eg, anxiety and depression) (Ref)

• Family history of impulse control disorders (Ref)

• Earlier onset of PD (Ref)

• Longer duration of PD (Ref)

• Alcohol use (Ref)

Nausea and vomiting

Nausea and vomiting are known side effects of dopamine agonists, such as ropinirole.

Mechanism: Dose-related; may be related to direct D₂ receptor agonism within the chemoreceptor trigger zone (Ref).

Onset: Commonly seen in early phase of treatment (Ref). It is important to note that reports of nausea and vomiting in studies may be subject to recall bias; so, it is unclear whether the onset of symptoms occurred with the first doses or required weeks of therapy prior to onset (Ref).

Risk factors (possible):

• Administration on an empty stomach (Ref)

• Use of IR formulations (Ref)

Orthostatic hypotension and syncope

Ropinirole may cause orthostatic hypotension. Patients with Parkinson disease (PD) may have an impaired capacity to respond to a postural change due to neurodegenerative processes in the brain stem. Orthostatic hypotension may be asymptomatic or symptomatic, leading to dizziness and falling (Ref). Syncope, sometimes associated with bradycardia, has also been observed in association with ropinirole in early Parkinson disease patients and patients with restless leg syndrome (RLS).

Mechanism: Primarily by venous and arterial dilation through inhibition of the sympathetic nervous system (Ref).

Onset: Varied; may occur at any point during treatment (Ref). Most cases occurred more than 4 weeks after initiation and may occur more often with initiation of therapy or dose escalation.

Risk factors:

• Initiation of therapy or dose escalation

• Autonomic dysfunction (as with PD) (Ref)

• Concurrent medications that may cause orthostatic hypotension (eg, antihypertensive or antiarrhythmic medications, diuretics, levodopa, monoamine oxidase inhibitors, tricyclic antidepressants) (Ref)

• Cardiovascular disease (eg, heart failure) (Ref)

• Hypovolemia (Ref)

• Younger patients with asthenic features (Ref)

Psychotic-like behavior

Ropinirole may cause or exacerbate behavioral changes, including psychotic symptoms (eg, paranoid ideation, hallucination, delusion, confusion, mania, disorientation, aggressive behavior, agitation, delirium). In a prospective comparison of levodopa versus ropinirole treatment, ropinirole demonstrated a higher incidence of hallucinations compared to levodopa (17% vs 6%) (Ref).

Mechanism: Dose- and duration-related; ropinirole is a non-ergot D₂/D₃ dopamine agonist with greatest affinity for D₃ receptors. Psychosis is thought to result from some degree of D₂ receptor stimulation (Ref).

Onset: Hallucinations typically occurred more frequently in adjunct studies versus early therapy studies for Parkinson disease (Ref).

Risk factors:

• Higher doses (Ref)

• Longer duration of therapy (Ref)

• Comorbid cognitive impairment or dementia (Ref)

• Older patients (hallucinations)

• Previous history of hallucinations (Ref)

• Number of comorbidities and concurrent medications (Ref)

Somnolence and sleep attacks

Somnolence (drowsiness) is an adverse reaction of dopamine agonists, including ropinirole (Ref). Patients taking ropinirole may experience sleep attacks (sudden onset of sleep), defined as sudden, irresistible, overwhelming sleepiness without awareness of falling sleep (Ref). Conversely, studies in patients with restless leg syndrome (RLS) found that ropinirole may improve sleep adequacy, quantity, and sleep disturbance, and reduce daytime somnolence (Ref). Sleep attacks may also occur in patients with Parkinson disease (PD) in the absence of dopaminergic medications (Ref).

Mechanism: Likely multifactorial; related to modulation of dopamine receptors, specifically D₃ agonist activity. May also be the result of increased dopamine, leading to down regulation of dopaminergic input to the reticular activating system. Genetic polymorphisms in dopamine receptors may play a role (Ref).

Onset: Delayed; some cases have occurred more than a year after initiation.

Risk factors:

• Longer treatment duration (Ref)

• Patients with PD (Ref)

• Depression in patients with PD (Ref)

• Disease duration <7 years (Ref)

• Age <70 years (Ref)

• History of sleep disorders (other than RLS)

• Concurrent alcohol or medications that may cause sedation or increase ropinirole plasma levels

Withdrawal syndrome

Dopamine agonist withdrawal syndrome (DAWS) has been defined as a stereotyped cluster of physical and psychological symptoms that may be mild, moderate, or severe. Psychiatric symptoms may include anxiety, panic attacks, depression, irritability, agitation, dysphoria, agoraphobia, insomnia, drug cravings, and pain. Physical symptoms may include diaphoresis, flushing, nausea, fatigue, orthostatic hypotension, and vomiting. Psychiatric symptoms are the most common and prominent symptoms (Ref). DAWS has been reported mainly in Parkinson disease, where it affects about 15% to 19% of patients who taper or discontinue a dopamine agonist (Yu 2017). Some recent case reports have identified this syndrome in patients with restless leg syndrome as well (Ref). Symptoms may be self-limited or protracted, lasting for months to years (Yu 2017).

Mechanism: Exact mechanism unknown; may be dose- and duration-related. May be due to sudden changes in dopaminergic stimulation (Ref).

Onset: Varied; may occur at any time during taper or after discontinuation (Ref).

Risk factors:

• Higher daily doses (≥7.5 mg/day) (Ref)

• Cumulative exposure to dopamine agonists (Ref)

• Presence of impulse control disorder (Ref)

• History of deep brain stimulation (Ref)

Adverse Reactions

The following adverse drug reactions and incidences are derived from product labeling as reported with the immediate-release (IR) and extended-release (ER) formulations. IR data are inclusive of trials in early Parkinson disease (PD) without levodopa and restless legs syndrome (RLS). Extended-release (ER) data are from trials in early PD without levodopa.

>10%:

Cardiovascular: Hypertension (IR: PD: 5%; ER: 3% to 15%), hypotension (IR: PD: 2%, RLS: ≤25%), orthostatic hypotension (IR: PD: 6%, RLS: ≤25%; ER: 14%) (table 1)Orthostatic Hypotension, syncope (IR: PD: 12%, RLS: 1% to 2%; ER: <1%; sometimes associated with bradycardia)

**Ropinirole: Adverse Reaction: Orthostatic Hypotension**
Drug (Ropinirole)	Placebo	Dosage Form	Indication	Number of Patients (Ropinirole)	Number of Patients (Placebo)	Comments
14%	10%	Extended-release tablets	Early Parkinson disease	N/A	N/A	Decrease in standing systolic blood pressure of ≥20 mm Hg
6%	5%	Immediate-release tablets	Early Parkinson disease	157	147	N/A
25%	0%	Immediate-release tablets	Restless legs syndrome	55	27	Hypotension or orthostatic hypotension
0.8%	0.4%	Immediate-release tablets	Restless legs syndrome	496	500	N/A

Gastrointestinal: Nausea (IR: PD: 60%, RLS: 40%; ER: 8% to 33%) (table 2)Nausea, vomiting (IR: PD: 12%, RLS: 11%; ER: ≤10%) (table 3)Vomiting

**Ropinirole: Adverse Reaction: Nausea**
Drug (Ropinirole)	Placebo	Dose	Dosage Form	Indication	Number of Patients (Ropinirole)	Number of Patients (Placebo)
60%	22%	N/A	Immediate-release tablets	Early Parkinson disease	157	147
33%	8%	8 mg/day	Extended-release tablets	Early Parkinson disease	40	40
15%	8%	4 mg/day	Extended-release tablets	Early Parkinson disease	41	40
15%	8%	24 mg/day	Extended-release tablets	Early Parkinson disease	13	40
10%	8%	12 mg/day	Extended-release tablets	Early Parkinson disease	39	40
8%	8%	2 mg/day	Extended-release tablets	Early Parkinson disease	13	40
40%	8%	N/A	Immediate-release tablets	Restless legs syndrome	496	500

**Ropinirole: Adverse Reaction: Vomiting**
Drug (Ropinirole)	Placebo	Dose	Dosage Form	Indication	Number of Patients (Ropinirole)	Number of Patients (Placebo)
12%	7%	N/A	Immediate-release tablets	Early Parkinson disease	157	147
10%	5%	8 mg/day	Extended-release tablets	Early Parkinson disease	40	40
5%	5%	4 mg/day	Extended-release tablets	Early Parkinson disease	41	40
0%	5%	2 mg/day	Extended-release tablets	Early Parkinson disease	13	40
0%	5%	12 mg/day	Extended-release tablets	Early Parkinson disease	39	40
0%	5%	24 mg/day	Extended-release tablets	Early Parkinson disease	13	40
11%	2%	N/A	Immediate-release tablets	Restless legs syndrome	496	500

Infection: Viral infection (IR: PD: 11%)

Nervous system: Dizziness (IR: PD: 40%, RLS: 11%; ER: ≤10%) (table 4)Dizziness, drowsiness (IR: PD: 40%, RLS: 12%; ER: 8% to 15%) (table 5)Drowsiness, fatigue (IR: PD: ≤16%, RLS: ≤9%), headache (ER: 5% to 15%), malaise (IR: PD: ≤16%, RLS: ≤9%)

**Ropinirole: Adverse Reaction: Dizziness**
Drug (Ropinirole)	Placebo	Dose	Dosage Form	Indication	Number of Patients (Ropinirole)	Number of Patients (Placebo)
40%	22%	N/A	Immediate-release tablets	Early Parkinson disease	157	147
10%	5%	8 mg/day	Extended-release tablets	Early Parkinson disease	40	40
8%	5%	12 mg/day	Extended-release tablets	Early Parkinson disease	39	40
8%	5%	24 mg/day	Extended-release tablets	Early Parkinson disease	13	40
5%	5%	4 mg/day	Extended-release tablets	Early Parkinson disease	41	40
0%	5%	2 mg/day	Extended-release tablets	Early Parkinson disease	13	40
11%	5%	N/A	Immediate-release tablets	Restless legs syndrome	496	500

**Ropinirole: Adverse Reaction: Drowsiness**
Drug (Ropinirole)	Placebo	Dose	Dosage Form	Indication	Number of Patients (Ropinirole)	Number of Patients (Placebo)
40%	6%	N/A	Immediate-release tablets	Early Parkinson disease	157	147
15%	5%	2 mg/day	Extended-release tablets	Early Parkinson disease	13	40
12%	5%	4 mg/day	Extended-release tablets	Early Parkinson disease	41	40
10%	5%	8 mg/day	Extended-release tablets	Early Parkinson disease	40	40
8%	5%	12 mg/day	Extended-release tablets	Early Parkinson disease	39	40
8%	5%	24 mg/day	Extended-release tablets	Early Parkinson disease	13	40
12%	6%	N/A	Immediate-release tablets	Restless legs syndrome	496	500

Neuromuscular & skeletal: Asthenia (IR: PD: ≤16%, RLS: ≤9%), back pain (ER: 5% to 15%)

1% to 10%:

Cardiovascular: Atrial fibrillation (IR: PD: 2%), chest pain (IR: PD: 4%), extrasystoles (IR: PD: 2%), flushing (IR: PD: 3%), lower extremity edema (IR: PD: 7%), palpitations (IR: PD: 3%), peripheral edema (IR: RLS: 2%), peripheral ischemia (IR: PD: 3%), tachycardia (IR: PD: 2%)

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

Endocrine & metabolic: Dependent edema (IR: PD: 6%)

Gastrointestinal: Abdominal pain (IR: PD: 6%; ER: 7%), anorexia (IR: PD: 4%), constipation (ER: 5%), diarrhea (IR: RLS: 5%), dyspepsia (IR: PD: 10%, RLS: 4%), flatulence (IR: PD: 3%), upper abdominal pain (IR: RLS: 3%), xerostomia (IR: PD: 5%, RLS: 3%)

Genitourinary: Impotence (IR: PD: 3%), urinary tract infection (IR: PD: 5%)

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

Infection: Influenza (IR: RLS: 3%)

Nervous system: Amnesia (IR: PD: 3%), confusion (IR: PD: 5%) (table 6)Confusion, hallucination (IR: PD: 5%) (table 7)Hallucination, hypoesthesia (IR: PD: 4%), lack of concentration (IR: PD: 2%), pain (IR: PD: 8%), paresthesia (IR: RLS: 3%), sudden onset of sleep (IR; ER: ≤10%) (table 8)Sudden Onset of Sleep, vertigo (IR: PD, RLS: 2%), yawning (IR: PD: 3%)

**Ropinirole: Adverse Reaction: Confusion**
Drug (Ropinirole)	Placebo	Dosage Form	Indication	Number of Patients (Ropinirole)	Number of Patients (Placebo)
5%	1%	Immediate-release tablets	Early Parkinson disease	157	147

**Ropinirole: Adverse Reaction: Hallucination**
Drug (Ropinirole)	Placebo	Dosage Form	Indication	Number of Patients (Ropinirole)	Number of Patients (Placebo)
5%	1%	Immediate-release tablets	Early Parkinson disease	157	147

**Ropinirole: Adverse Reaction: Sudden Onset of Sleep**
Drug (Ropinirole)	Placebo	Dose	Dosage Form	Indication	Number of Patients (Ropinirole)	Number of Patients (Placebo)
10%	0%	12 mg/day	Extended-release tablets	Early Parkinson disease	39	40
8%	0%	24 mg/day	Extended-release tablets	Early Parkinson disease	13	40
5%	0%	4 mg/day	Extended-release tablets	Early Parkinson disease	41	40
0%	0%	2 mg/day	Extended-release tablets	Early Parkinson disease	13	40
0%	0%	8 mg/day	Extended-release tablets	Early Parkinson disease	40	40

Neuromuscular & skeletal: Arthralgia (IR: RLS: 4%), hyperkinetic muscle activity (IR: PD: 2%), increased creatine phosphokinase in blood specimen (ER: 10%), limb pain (IR: RLS: 3%), muscle cramps (IR: RLS: 3%)

Ophthalmic: Eye disease (IR: PD: 3%), visual disturbance (IR: PD: 6%), xerophthalmia (IR: PD: 2%)

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

<1%: Respiratory: Pleural effusion

Postmarketing (all indications and formulation):

Cardiovascular: Heart valve disease (Andersohn 2009, Dewey 2007)

Nervous system: Aggressive behavior, agitation, behavioral problems, delirium, delusion, disorientation, falling (Kujawa 2000), impulse control disorder (including increased libido, pathological gambling) (Bastiaens 2013; Corvol 2018), mania, paranoid ideation, psychotic symptoms (Grover 2010), restless legs syndrome (IR: RLS: augmentation and/or early morning rebound) (García-Borreguero 2012, Rosenstein 2015), withdrawal syndrome (including anxiety, apathy, depression, insomnia) (Yu 2017)

Respiratory: Interstitial pulmonary disease, pleuropulmonary fibrosis (Andersohn 2009)

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.

• 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.

• 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.

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).

• Psychotic disorder: Avoid use in patients with a major psychotic disorder; may exacerbate symptoms.

• Renal impairment: Use with caution in patients with severe kidney impairment.

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.

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

Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.

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 used at chemotherapy doses, hold blood pressure lowering medications for 24 hours before amifostine administration. If blood pressure lowering therapy cannot be held, do not administer amifostine. Use caution with radiotherapy doses of amifostine. Risk D: Consider therapy modification

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

Amisulpride (Oral): May diminish the therapeutic effect of Anti-Parkinson Agents (Dopamine Agonist). Anti-Parkinson Agents (Dopamine Agonist) may diminish the therapeutic effect of Amisulpride (Oral). 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. 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). Risk D: 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). 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

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

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

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

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

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

Herbal Products with Blood Pressure Lowering Effects: 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

Kava Kava: May enhance the adverse/toxic effect of Anti-Parkinson Agents (Dopamine Agonist). Kava Kava may diminish the therapeutic effect of Anti-Parkinson Agents (Dopamine Agonist). 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

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

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

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

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

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

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

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

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).

Breastfeeding 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 breastfeed during therapy should consider the risk of infant exposure, the benefits of breastfeeding to the infant, and benefits of treatment to the mother.

Monitoring Parameters

BP (orthostatic); signs and symptoms of postural hypotension, especially during dose escalation (Parkinson patients); daytime alertness; CNS depression, fall risk, behavior changes (eg, compulsive behaviors); periodic skin examinations

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 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.

Pharmacokinetics

Absorption: Immediate release: Rapid

Distribution: V_d: 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; T_max increased by 2.5-3 hours when taken with a high-fat meal

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

Pharmacokinetics: Additional Considerations

Altered kidney function: 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

Older adult: 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. C_max was 30% and AUC was 38% lower in smokers compared with nonsmokers.

Pricing: US

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 (rOPINIRole HCl Oral)

0.25 mg (per each): $0.20 - $2.52

0.5 mg (per each): $0.20 - $2.52

1 mg (per each): $0.20 - $2.52

2 mg (per each): $0.20 - $2.52

3 mg (per each): $0.23 - $2.62

4 mg (per each): $0.23 - $2.62

5 mg (per each): $0.23 - $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.

Brand Names: International

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

For country code abbreviations (show table)

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