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rOPINIRole

Brand name: Requip
Drug class: Nonergot-derivative Dopamine Receptor Agonists
- Antiparkinsonian Agents
VA class: CN500
Chemical name: 4-[2-(Dipropylamino)ethyl]-1,3-dihydro-2(H)-indol-2-one monohydrochloride
Molecular formula: C16H24N2O•ClH
CAS number: 91374-20-8

Medically reviewed by Drugs.com on May 5, 2022. Written by ASHP.

Introduction

Nonergot-derivative dopamine receptor agonist.

Uses for rOPINIRole

Parkinsonian Syndrome

Symptomatic management of parkinson disease.

Used as monotherapy in patients with early disease or as an adjunct to levodopa in patients with advanced disease.

Levodopa is currently the most effective drug for relieving motor symptoms of parkinson disease. However, effectiveness of levodopa decreases over time and most patients develop motor complications (e.g., wearing-off symptoms, dyskinesias) with long-term use. Strategies to reduce these complications include adjusting dosage of levodopa, adding other antiparkinsonian agents (e.g., dopamine receptor agonists), or initiating other agents first to delay use of levodopa.

Restless Legs Syndrome

Symptomatic management of moderate-to-severe primary restless legs syndrome (RLS; Willis-Ekbom disease).

Nonergot-derivative dopamine receptor agonists (e.g., pramipexole, ropinirole, rotigotine) are considered one of several drugs of choice for reducing symptoms of RLS.

rOPINIRole Dosage and Administration

Administration

Administer orally as conventional (immediate-release) or extended-release tablets. Extended-release tablets are FDA-labeled for use only in the treatment of parkinson disease. Both formulations may be administered without regard to food.

Oral Administration

Immediate-release Tablets

Administer orally in 3 equally divided doses daily for treatment of parkinson disease.

Administer once daily 1–3 hours before bedtime for treatment of RLS.

Extended-release Tablets

Administer once daily.

Swallow tablets whole; do not chew, crush, or divide.

Extended-release tablet is designed to release drug over a 24-hour period; if rapid GI transit occurs, incomplete release may occur, causing some tablet residue to appear in the stool.

Possible Prescribing and Dispensing Errors

Ensure accuracy of prescription; similarities in both the trade (brand) and generic (nonproprietary) names, similarities in container labels and carton packaging, illegible handwriting on prescriptions, and overlapping product characteristics (e.g., drug strengths, dosage forms, dosage intervals) between risperidone (Risperdal, an antipsychotic agent) and ropinirole hydrochloride (Requip) may result in medication errors. These errors have required hospitalization in some cases.

Dosage

Available as ropinirole hydrochloride; dosage expressed in terms of ropinirole.

Initiate with low dosage and increase slowly based on clinical response and tolerability.

If therapy is interrupted for a substantial period of time, retitration may be warranted.

Adults

Parkinson Disease
Oral
Immediate-release Tablets

Initially, 0.25 mg 3 times daily; if needed, increase in weekly increments based on response and tolerability up to maximum daily dosage of 24 mg. The manufacturer recommends the following dosage titration schedule in Table 1.

Table 1. Dosage Titration Schedule for Ropinirole (Immediate-release Tablets) in the Treatment of Parkinson Disease1

Week of Therapy

Daily Dosage Schedule

Total Daily Dose

1

0.25 mg 3 times daily

0.75 mg

2

0.5 mg 3 times daily

1.5 mg

3

0.75 mg 3 times daily

2.25 mg

4

1 mg 3 times daily

3 mg

After week 4

If necessary, dosage may be increased by 1.5 mg daily each week up to 9 mg daily, and then by up to 3 mg daily each week up to a total maximum recommended daily dosage of 24 mg

Continually re-evaluate and adjust dosage according to the needs of the patient in an effort to find a dosage that provides maximum relief of symptoms with minimum adverse effects.

When discontinuing therapy, gradually reduce dosage over a period of 1 week. Reduce frequency of administration from 3 times daily to twice daily for 4 days and then to once daily for 3 days before complete discontinuance of the drug.

Concomitant therapy with ropinirole and levodopa may cause or exacerbate preexisting dyskinesia; dosage reduction of the dopaminergic agents may alleviate this effect.

Extended-release Tablets
Oral

Initially, 2 mg once daily for 1–2 weeks; if needed, increase dosage by increments of 2 mg daily at weekly (or longer) intervals based on patient response and tolerability.

Monitor patients weekly during titration period and adjust dosage to provide maximum relief of symptoms with minimum adverse effects.

Although maximum recommended dosage is 24 mg daily, manufacturer recommends lower maintenance dosages. (See Prescribing Limits under Dosage and Administration.)

When discontinuing therapy, gradually reduce dosage over a period of 1 week.

Concomitant therapy with ropinirole and levodopa may cause or exacerbate preexisting dyskinesia; dosage reduction of the dopaminergic agents may alleviate this effect.

Switching from Immediate-release to Extended-release Tablets
Oral

May switch patients directly from immediate-release tablets to extended-release tablets at the same approximate total daily dosage (see Table 2). Following conversion, adjust dosage if necessary based on patient response and tolerability.

Table 2. Conversion from Immediate-release to Extended-release Ropinirole Tablets30

Immediate-release Tablets (Total Daily Dose in mg)

Extended-release Tablets (Total Daily Dose in mg)

0.75–2.25

2

3–4.5

4

6

6

7.5–9

8

12

12

15

16

18

18

21

20

24

24

Restless Legs Syndrome
Oral

Initially, 0.25 mg once daily 1–3 hours before bedtime as immediate-release tablets. May increase dosage after 2 days if necessary based on patient response and tolerability, up to maximum of 4 mg daily (see Table 3).

Table 3 Dosage Titration Schedule for Ropinirole (Immediate-release Tablets) in the Treatment of RLS1

Day/Week of Therapy

Daily Dosage (given once daily before bedtime)

Days 1 and 2

0.25 mg

Days 3–7

0.5 mg

Week 2

1 mg

Week 3

1.5 mg

Week 4

2 mg

Week 5

2.5 mg

Week 6

3 mg

Week 7

4 mg

When discontinuing therapy, gradually reduce dosage.

Prescribing Limits

Adults

Parkinson Disease
Immediate-release Tablets
Oral

Maximum recommended dosage is 24 mg daily (administered as 8 mg 3 times daily); dosages >24 mg daily not evaluated in clinical trials.

Extended-release Tablets
Oral

Maximum recommended dosage is 24 mg daily. However, manufacturer states that patients with advanced parkinson disease should generally be maintained at dosages ≤8 mg daily and patients with early parkinson disease should generally be maintained at dosages ≤12 mg daily; higher dosages not shown to provide greater benefit and may increase risk of adverse effects.

Restless Legs Syndrome
Oral

Maximum recommended dosage is 4 mg once daily (as immediate-release tablets); safety and efficacy of higher dosages not established.

Special Populations

Hepatic Impairment

Manufacturers make no specific recommendations for dosage adjustment.

Renal Impairment

Parkinson Disease

No dosage adjustment necessary in patients with moderate renal impairment (Clcr 30–50 mL/minute).

In patients with end-stage renal disease undergoing hemodialysis, recommended initial dosage is 0.25 mg 3 times daily (as immediate-release tablets) or 2 mg once daily (as extended-release tablets); may increase dosage based on patient response and tolerability up to maximum total daily dosage of 18 mg. Supplemental doses not required after dialysis.

Not evaluated in patients with severe renal impairment not undergoing regular dialysis.

Restless Legs Syndrome

No dosage adjustment necessary in patients with moderate renal impairment (Clcr 30–50 mL/minute).

In patients with end-stage renal disease undergoing hemodialysis, recommended initial dosage is 0.25 mg once daily (as immediate-release tablets); may increase dosage based on patient response and tolerability up to a maximum total daily dosage of 3 mg. Supplemental doses not required after dialysis.

Not evaluated in patients with severe renal impairment not undergoing regular dialysis.

Geriatric Patients

No dosage adjustments necessary in patients >65 years of age since dosage is individualized and titrated according to clinical response.

Cautions for rOPINIRole

Contraindications

  • Known hypersensitivity to ropinirole hydrochloride or any ingredient in the formulation.

Warnings/Precautions

Warnings

Falling Asleep During Activities of Daily Living and Somnolence

Episodes of falling asleep while engaged in activities of daily living (e.g., driving) reported; sometimes resulted in accidents. Reported as late as 1 year after initiation of ropinirole therapy.

Some patients perceived no warning signs (e.g., excessive drowsiness) and believed they were alert immediately prior to the event. Falling asleep while engaged in such activities usually occurs in a setting of preexisting somnolence, although patients may not give such a history.

Somnolence commonly occurs in patients receiving ropinirole and is more frequent in patients with parkinson disease than in patients with RLS.

Continually reassess patients for drowsiness or sleepiness. Patients may not acknowledge drowsiness or sleepiness until directly questioned about such adverse effects during specific activities. Ask patients about any factors that may increase the risk of somnolence (e.g., concomitant sedating drugs, presence of sleep disorders, concomitant drugs that increase plasma ropinirole concentrations).

In general, discontinue therapy if a patient develops daytime sleepiness or episodes of falling asleep during activities that require active participation (e.g., conversations, eating). If the drug is continued, advise patient not to drive and to avoid other potentially dangerous activities. Insufficient information to establish whether dosage reduction will eliminate this adverse event.

Syncope

Syncope, sometimes associated with bradycardia, reported. Most cases occurred >4 weeks after initiation of therapy and were associated with a recent dosage increase.

Patients with significant cardiovascular disease were excluded from clinical studies; use caution in such patients.

Hypotension and Orthostatic Hypotension

Dopaminergic agents appear to impair systemic regulation of BP, which can cause orthostatic hypotension, especially during dosage escalation. Orthostatic hypotension can also be a manifestation of parkinson disease.

Substantial hypotension not related to standing reported with extended-release ropinirole.

Carefully monitor patients for manifestations of orthostatic hypotension, especially during dosage escalation.

Hallucinations/Psychotic-like Behavior

Potential for hallucinations in patients with parkinson disease; increased risk observed in geriatric patients and those receiving concomitant levodopa.

During postmarketing experience, other new or worsening mental status and behavioral changes (e.g., paranoid ideation, delusions, hallucinations, confusion, psychotic-like behavior, disorientation, aggressive behavior, agitation, delirium) reported during therapy or after initiating or increasing dosage. Other antiparkinsonian agents can produce similar effects.

Use generally not advised in patients with a major psychotic disorder. Concomitant use with antipsychotic agents may exacerbate parkinsonian symptoms and decrease effectiveness of ropinirole.

Dyskinesia

May cause or exacerbate preexisting dyskinesia in patients with parkinson disease receiving concomitant levodopa. Dosage reduction of the dopaminergic agents may alleviate this effect.

Impulse Control/Compulsive Behaviors

Intense urges and compulsive behaviors (e.g., urge to gamble, increased sexual urges, binge eating, uncontrolled spending, other intense urges) and inability to control these urges reported in some patients receiving dopaminergic agents. In some cases, urges stopped when dosage was reduced or drug was discontinued.

Consider reducing dosage or discontinuing ropinirole if a patient develops such behaviors.

Hyperpyrexia and Confusion

A symptom complex resembling neuroleptic malignant syndrome (NMS; e.g., elevated temperature, muscular rigidity, altered consciousness, autonomic instability) reported in association with rapid dosage reduction of, withdrawal of, or changes in dopaminergic therapy.

Gradually withdraw therapy at the end of treatment.

Melanoma

Melanoma observed more frequently in patients with parkinson disease than in the general population. In clinical studies, one patient who received extended-release ropinirole and who also was receiving levodopa/carbidopa developed melanoma.

Monitor for melanoma on a frequent and regular basis. Periodic dermatologic screening is recommended.

Augmentation and Rebound in Restless Legs Syndrome

Long-term use of dopaminergic agents in patients with RLS associated with augmentation (i.e., worsening of symptoms during treatment); can manifest as an increase in overall symptom severity, earlier time of symptom onset each day, or extension of symptoms to other extremities. Augmentation reported during postmarketing experience with ropinirole.

Rebound (i.e., new onset of symptoms in the early morning hours) also reported during postmarketing experience.

If augmentation or rebound occurs, consider dosage adjustment or discontinuance of therapy; when discontinuing therapy, reduce dosage gradually whenever possible.

Fibrotic Effects

Fibrotic complications, including retroperitoneal fibrosis, pulmonary infiltrates, pleural effusion, pleural thickening, pericarditis, and/or cardiac valvulopathy, reported with ergot-derivative dopamine receptor agonists; presumably related to the ergoline structure of these compounds. Not known whether nonergot-derivative dopamine agonists, can also cause such fibrotic reactions.

Cases of possible fibrotic complications (e.g., pleural effusion or fibrosis, interstitial lung disease, cardiac valvulopathy) reported in clinical trials and during postmarketing experience with ropinirole. Causal relationship not established; however, possibility of contributory role of drug cannot be excluded.

Ocular Effects

Retinal degeneration reported in albino rats treated with ropinirole for 2 years; similar changes not observed in other animal species or in albino rats treated for 1 year. Clinical importance in humans not established.

A 2-year study in patients with parkinson disease did not reveal any clinically important differences with regard to retinal effects between ropinirole and levodopa.

Binding to Melanin

Ropinirole binds to melanin-rich tissues (e.g., eye, skin) in pigmented rats after a single dose; retention of drug was demonstrated with a half-life of 20 days in the eye.

Specific Populations

Pregnancy

No adequate data in pregnant women. In animal studies, adverse developmental effects (e.g., teratogenicity, embyrolethality) observed.

Lactation

Distributed into milk in rats. Not known whether the drug is distributed into human milk, affects milk production, or affects the breast-fed infant.

Consider known benefits of breast-feeding along with mother's clinical need for ropinirole and any potential adverse effects on the breast-fed infant from drug or underlying maternal condition.

Ropinirole inhibits prolactin secretion and can potentially inhibit lactation.

Pediatric Use

Safety and efficacy not established in pediatric patients.

Geriatric Use

In clinical studies in patients with parkinson disease, some adverse effects were more frequent in geriatric patients (e.g., hallucinations, vomiting, nausea) than in younger patients receiving the drug.

Hepatic Impairment

Clearance may be reduced.

Renal Impairment

Clearance is reduced in patients with end-stage renal disease undergoing hemodialysis; reduced dosage recommended.

Not evaluated in patients with severe renal impairment (ClCr <30 mL/minute) who are not undergoing hemodialysis.

Common Adverse Effects

Patients with early parkinson disease receiving immediate-release tablets (without levodopa): Nausea, somnolence, dizziness, syncope, asthenic condition, viral infection, leg edema, vomiting, dyspepsia.

Patients with early parkinson disease receiving extended-release tablets: Nausea, somnolence, sudden onset of sleep, hypertension, headache, abdominal pain/discomfort, dizziness, constipation.

Patients with advanced parkinson disease receiving immediate-release tablets (with concomitant levodopa): Dyskinesia, somnolence, nausea, dizziness, confusion, hallucinations, sweating, headache.

Patients with advanced parkinson disease receiving extended-release tablets: Nausea, dyskinesia, dizziness, hallucinations.

Patients with RLS receiving immediate-release tablets: Nausea, somnolence, vomiting, dizziness, fatigue.

Interactions for rOPINIRole

Drugs Affecting Hepatic Microsomal Enzymes

Metabolized principally by CYP1A2. Does not inhibit or induce CYP isoenzymes.

CYP1A2 inhibitors (e.g., ciprofloxacin, fluvoxamine, mexiletine, norfloxacin) and CYP1A2 inducers (e.g., omeprazole): May alter clearance of ropinirole. If a potent CYP1A2 inhibitor or inducer is initiated or discontinued during ropinirole therapy, dosage adjustment of ropinirole may be required.

CYP substrates: Pharmacokinetic interactions not likely.

Dopamine Antagonists

Possible pharmacodynamic interaction, resulting in diminished effectiveness of ropinirole.

Specific Drugs

Drug

Interaction

Comments

Amantadine

Alteration of ropinirole clearance is unlikely

Anticholinergic agents

Alteration of ropinirole clearance is unlikely

Antidepressants, tricyclics

Alteration of ropinirole clearance is unlikely

Antihistamines

Alteration of ropinirole clearance is unlikely

Antipsychotic agents

May exacerbate symptoms of parkinson disease and diminish effectiveness of ropinirole

Benzodiazepines

Alteration of ropinirole clearance is unlikely

Cigarette smoking

Smoking (which is known to induce CYP1A2) is expected to increase clearance of ropinirole

Ciprofloxacin

Increased peak plasma concentration and AUC of ropinirole

Dosage adjustment of ropinirole may be required when ciprofloxacin is initiated or discontinued

CNS depressants (e.g., alcohol)

Possible additive sedative effects

Use with caution

Digoxin

Pharmacokinetics of digoxin not altered

Estrogens (e.g., ethinyl estradiol)

High dosages of estrogens (e.g., those used for hormone replacement therapy) may reduce oral clearance of ropinirole

If estrogen therapy is initiated or discontinued during treatment with ropinirole, dosage adjustment of ropinirole may be required

Ibuprofen

Alteration of ropinirole clearance is unlikely

Levodopa

May increase the risk of dyskinesia in patients with parkinson disease

No effect on steady-state pharmacokinetics of ropinirole; peak plasma concentrations of levodopa increased by 20%, but systemic exposure not affected

Selegiline

Alteration of ropinirole clearance is unlikely

Thiazide diuretics

Alteration of ropinirole clearance is unlikely

Theophylline

Pharmacokinetics of both drugs unaffected

rOPINIRole Pharmacokinetics

Absorption

Bioavailability

Rapidly absorbed after oral administration, with peak plasma concentration attained in approximately 1–2 hours.

Appears to undergo first-pass metabolism; absolute bioavailability is about 55%.

Food

Food decreases the rate but not the extent of absorption; time to peak plasma concentration is delayed by about 2.5 hours and peak plasma concentration is reduced.

Distribution

Extent

Widely distributed throughout the body.

Plasma Protein Binding

Up to 40%.

Elimination

Metabolism

Extensively metabolized in the liver by N-despropylation and hydroxylation to form inactive metabolites. Metabolism is mediated principally by CYP1A2.

Elimination Route

Excreted in urine principally as metabolites; <10% of an administered dose is excreted in urine as unchanged drug.

Half-life

Approximately 6 hours.

Special Populations

In patients >65 years of age, oral clearance of ropinirole is reduced by 15%.

Pharmacokinetics not evaluated in patients with hepatic impairment; however, clearance may be reduced and plasma concentrations increased.

Pharmacokinetics not altered in patients with moderate renal impairment (Clcr 30–50 mL/minute). Not evaluated in patients with severe renal impairment (Clcr <30 mL/minute) who are not undergoing hemodialysis.

Stability

Storage

Oral

Immediate-release Tablets

Tightly closed container at room temperature of 20–25°C (may be exposed to 15–30°C). Protect from light and moisture.

Extended-release Tablets

Tightly closed, light-resistant container at 20–25°C (may be exposed to 15–30°C).

Actions

  • Exhibits high binding specificity for and intrinsic activity at dopamine D2 receptors in vitro compared with other dopamine receptor agonists (e.g., bromocriptine, pergolide); has a higher affinity for the D3 subtype than for the D2 or D4 subtypes.

  • Parkinson disease: Appears to act by directly stimulating postsynaptic dopamine receptors in the corpus striatum.

  • RLS: Mechanism of action of ropinirole is unknown. The dopaminergic system appears to be involved in the pathogenesis of this syndrome.

Advice to Patients

  • Importance of reading the manufacturer's patient information.

  • Importance of taking ropinirole as prescribed; if a dose is missed, advise patient not to double next dose. Advise patients that ropinirole may be taken with or without food. Advise patients to contact their clinician if they wish to discontinue therapy or decrease dosage.

  • Risk of hypersensitivity reactions; importance of advising patients to immediately contact their clinician if they experience any manifestations of such reactions (e.g., urticaria, angioedema, rash, pruritus).

  • Importance of advising patients of the potential for sedating effects, including somnolence and the possibility of falling asleep while engaged in activities of daily living. Patients should avoid driving, operating machinery, or engaging in other potentially dangerous activities until effects on the individual are known. Importance of advising patients that if increased somnolence or episodes of falling asleep during activities of daily living (e.g., conversations, eating, driving) occur at any time during therapy, they should not drive or participate in potentially dangerous activities until they have contacted their clinician.

  • Potential for hypotension or orthostatic hypotension with or without symptoms (e.g., dizziness, nausea, syncope, sweating), especially during dosage escalation. Patients should avoid rising rapidly after sitting or lying down, especially if they have been in a seated or recumbent position for prolonged periods and/or if they are just beginning ropinirole therapy.

  • Risk of hallucinations, particularly in geriatric patients with parkinson disease, those receiving concomitant levodopa, and those receiving higher dosages of ropinirole.

  • Importance of informing patients with RLS that augmentation and rebound may occur.

  • Importance of informing patients of the risk of new onset or exacerbation of dyskinesia.

  • Importance of asking patients whether they have developed any new or increased urges or compulsive behaviors (e.g., gambling urges, sexual urges, uncontrolled spending, binge eating) while receiving ropinirole and of advising them of the importance of reporting such urges.

  • Importance of informing patients of the risk of new onset or exacerbation of dyskinesia.

  • Importance of informing clinician of existing or contemplated concomitant therapy, including prescription and OTC drugs (especially CNS depressants or alcohol), as well as any concomitant illnesses.

  • Importance of women informing their clinician if they are or plan to become pregnant or plan to breast-feed.

  • Importance of informing patients of other important precautionary information. (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

rOPINIRole Hydrochloride

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Tablets, film-coated

0.25 mg (of ropinirole)*

Requip Tiltab

GlaxoSmithKline

Ropinirole Tablets

0.5 mg (of ropinirole)*

Requip Tiltab

GlaxoSmithKline

Ropinirole Tablets

1 mg (of ropinirole)*

Requip Tiltab

GlaxoSmithKline

Ropinirole Tablets

2 mg (of ropinirole)*

Requip Tiltab

GlaxoSmithKline

Ropinirole Tablets

3 mg (of ropinirole)*

Requip Tiltab

GlaxoSmithKline

Ropinirole Tablets

4 mg (of ropinirole)*

Requip Tiltab

GlaxoSmithKline

Ropinirole Tablets

5 mg (of ropinirole)*

Requip Tiltab

GlaxoSmithKline

Ropinirole Tablets

Tablets, film-coated, extended-release

2 mg (of ropinirole)*

Requip XL

GlaxoSmithKline

rOPINIRole Extended-release Tablets

4 mg (of ropinirole)*

Requip XL

GlaxoSmithKline

rOPINIRole Extended-release Tablets

6 mg (of ropinirole)*

Requip XL

GlaxoSmithKline

rOPINIRole Extended-release Tablets

8 mg (of ropinirole)*

Requip XL

GlaxoSmithKline

rOPINIRole Extended-release Tablets

12 mg (of ropinirole)*

Requip XL

GlaxoSmithKline

rOPINIRole Extended-release Tablets

AHFS DI Essentials™. © Copyright 2023, Selected Revisions May 5, 2022. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.

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