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Ropinirole Hydrochloride

Pronunciation

Pronunciation: roe-PIN-i-ROLE HYE-droe-KLOR-ide
Class: Non-ergot dopamine receptor agonist

Trade Names

Requip
- Tablets 0.25 mg
- Tablets 0.5 mg
- Tablets 1 mg
- Tablets 2 mg
- Tablets 3 mg
- Tablets 4 mg
- Tablets 5 mg

Requip XL
- Tablets, extended-release 2 mg
- Tablets, extended-release 4 mg
- Tablets, extended-release 8 mg

Pharmacology

Precise mechanism of action in treatment for Parkinson disease unknown; believed to be caused by stimulation of postsynaptic dopamine D 2 -type receptors in the caudate-putamen in the brain.

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Mechanism of action as treatment for restless legs syndrome (RLS) is unknown.

Pharmacokinetics

Absorption

T max is 1 to 2 h. High-fat meal increases T max by 2.5 h and reduces C max by 25%, but does not affect extent of absorption. Absolute bioavailability is 55%. Steady state is reached within 2 days.

Extended-release

Bioavailability is 45% to 55%. Steady state is reached within 4 days. T max is 6 to 10 h.

Distribution

Widely distributed; Vd is 7.5 L/kg. Up to 40% protein bound.

Metabolism

Extensively metabolized in liver to inactive metabolites; CYP1A2 is major enzyme involved in metabolism.

Elimination

Eliminated in urine (less than 10% as unchanged drug). Elimination half-life is approximately 6 h. Cl is 47 L/h.

Special Populations

Renal Function Impairment

No difference in pharmacokinetics in patients with moderate renal function impairment compared with patients with CrCl above 50 mL/min. Effect of severe renal function impairment has not been studied.

Hepatic Function Impairment

Pharmacokinetics have not been evaluated.

Elderly

In patients older than 65 yr of age receiving immediate-release or extended-release formulations, oral Cl is reduced by approximately 30% or 15%, respectively, compared with younger patients. However, dosage adjustment is not necessary.

Cigarette smoking

Smoking is expected to increase the Cl of ropinirole because CYP1A2 is known to be induced by smoking. C max was 30% and AUC was 38% lower in smokers compared with nonsmokers.

Indications and Usage

Treatment of the signs and symptoms of idiopathic Parkinson disease; treatment of moderate to severe primary RLS (immediate-release only).

Contraindications

Standard considerations.

Dosage and Administration

Parkinson Disease

Individualize by careful titration.

Adults Immediate-release

PO 0.25 mg 3 times daily initially. Based on response, dosage may be increased weekly by 0.25 mg/day up to 3 mg/day, then by 1.5 mg/day up to 9 mg/day, then by 3 mg/day to total dose of 24 mg/day.

Extended-release

PO Start with 2 mg once daily for 1 to 2 wk, followed by increases of 2 mg/day at 1-wk intervals as appropriate, depending on therapeutic response and tolerability (max, 24 mg/day). Patients may be switched directly from immediate-release. The initial dose of the ER formulation should most closely match the total daily dose of the immediate-release formulation. Following conversion, the dose may be adjusted depending on therapeutic response and tolerability.

RLS
Adults

PO 0.25 mg once daily 1 to 3 h before bedtime. After 2 days, dose may be increased to 0.5 mg once daily, then to 1 mg once daily at end of first wk; dose may then be increased in 0.5 mg/day increments weekly for 5 additional wk, and then by 1 mg/day after 6 wk (max, 4 mg once daily).

General Advice

  • To discontinue the immediate-release tablets in patients with Parkinson disease, reduce frequency from 3 times daily to twice daily for 4 days then once daily for 3 days, then stop.
  • Discontinue the ER tablets gradually over 7 days.
  • Administer without regard to meals. Administer with food if GI upset occurs.
  • Do no chew, crush, or divide the ER tablets; swallow whole.
  • If a dose is missed, skip that dose and administer the next dose at the regularly scheduled time. Never double the dose to catch up.

Storage/Stability

Immediate-release

Store at controlled room temperature (68° to 77°F). Protect from light and moisture.

ER

Store at 59° to 86°F. Protect from light.

Drug Interactions

CNS depressants (eg, alcohol)

Use with caution because of additive CNS effects.

CYP1A2 inducers (eg, cigarette smoking, rifampin)

May increase metabolic Cl of ropinirole.

CYP1A2 inhibitors (eg, ciprofloxacin, erythromycin, fluvoxamine)

May decrease metabolic Cl of ropinirole.

Dopamine antagonists (eg, butyrophenones, metoclopramide, phenothiazines, thioxanthenes)

May reduce effectiveness of ropinirole.

Estrogen

May reduce Cl of ropinirole.

Levodopa

Ropinirole mat potentiate dopaminergic adverse reactions of levodopa, and may cause or exacerbate preexisting dyskinesias.

Warfarin

An increase in INR was reported in a patient stabilized on warfarin 9 days after starting ropinirole.

Laboratory Test Interactions

None well documented.

Adverse Reactions

Cardiovascular

Syncope (12%); orthostatic hypotension (6%); hypertension (5%); palpitation, peripheral ischemia (3%); atrial fibrillation, extrasystole, hypotension, tachycardia (2%); bradycardia, hot flush (at least 1%).

CNS

Dizziness, somnolence (40%); dyskinesia (34%); headache (17%); fatigue (11%); hallucinations (10%); confusion (9%); anxiety, asthenia, tremor (6%); amnesia, hypokinesia, nervousness, paresthesia (5%); hypesthesia, vertigo (4%); abnormal dreaming, malaise, paresis, yawning (3%); hyperkinesia, impaired concentration (2%); aggravated Parkinsonism, depression, dystonia, hypoesthesia, insomnia, irritability, migraine, neuralgia, sleep disorder (at least 1%); impulse control symptoms, increased libido including hypersexuality, pathological gambling (postmarketing).

Dermatologic

Increased sweating (7%); flushing (3%); night sweats, rash (at least 1%).

EENT

Nasopharyngitis (9%); abnormal vision, pharyngitis (6%); rhinitis (4%); eye abnormality (3%); diplopia, nasal congestion, xerophthalmia (2%); pharyngolaryngeal pain (at least 1%).

GI

Nausea (60%); vomiting (12%); dyspepsia (10%); abdominal pain (9%); abdominal pain/discomfort, constipation (6%); diarrhea, dry mouth (5%); anorexia (4%); upper abdominal pain, flatulence (3%); dysphagia, increased salivation (2%); gastroenteritis, gastroesophageal reflux disease, gingivitis, stomach discomfort, tooth abscess, tooth ache, viral gastroenteritis (at least 1%).

Genitourinary

UTI (6%); impotence (3%); pyuria, urinary incontinence (2%); erectile dysfunction, hematuria (at least 1%).

Metabolic-Nutritional

Increased alkaline phosphatase (3%); weight decrease (2%); hyperglycemia, increased BUN (at least 1%).

Musculoskeletal

Arthralgia (7%); arthritis, back pain, extremity pain, muscle cramp (3%); RLS (at least 2%); arthrosis, leg cramp, muscle spasm, muscle stiffness, myalgia, neck pain, osteoarthritis, rigors, tendonitis (at least 1%).

Respiratory

Upper respiratory tract infection (9%); sinusitis (4%); bronchitis, cough, dyspnea (3%); asthma, lower respiratory tract infection (at least 1%).

Miscellaneous

Viral infection (11%); falls (10%); pain (8%); increased drug level, leg edema (7%); dependent edema (6%); chest pain, peripheral edema (4%); hyperhidrosis, influenza (3%); anemia (2%); basal cell carcinoma, gout, influenza-like illness (at least 1%).

Precautions

Pregnancy

Category C .

Lactation

Undetermined.

Children

Safety and efficacy not established.

Elderly

Incidence of hallucinations appears to be increased with age.

Hepatic Function

Titrate ropinirole with caution in patients with hepatic function impairment.

Augmentation and rebound in RLS

Treatment of RLS can result in rebound (worsening of symptoms in early morning hours) and/or augmentation (earlier onset of symptoms in evening or afternoon, increase in symptoms, and spread of symptoms to involve other extremities).

Cardiovascular disease

Use with caution in patients with severe CV disease.

Falling asleep

Falling asleep during activities of daily living, including driving, has been reported. Consider discontinuation of therapy in patients who develop significant daytime sleepiness or episodes of falling asleep during activities that require active participation (eg, conversations, eating). If therapy is continued in such patients, caution patients not to drive and to avoid other potentially hazardous activities.

Fibrotic complications

A small number of cases of possible fibrotic complications, including cardiac valvulopathy, interstitial lung disease, pleural effusion, and pleural fibrosis, have been reported.

Hallucinations

Can occur during ropinirole therapy.

Hypotension

Postural hypotension may occur, especially during dose escalation.

Impulse control

Impulse control symptoms, including compulsive behavior, such as pathological gambling and hypersexuality, have been reported.

Major psychotic disorders

Major psychotic disorders may be exacerbated.

Melanoma

Patients with Parkinson disease have a higher risk of developing melanoma than the general population.

Syncope

Syncope, sometimes associated with bradycardia, has been observed. Most events occur more than 4 wk after starting therapy and are usually associated with a recent increase in dose.

Overdosage

Symptoms

Agitation, asthenia, chest pain, chorea, claustrophobia, confusional state, dizziness, dyskinesia, fatigue, hyperhidrosis, increased coughing, nausea, nightmares, orthostatic hypotension, palpitation, somnolence, syncope, vasovagal syncope, visual hallucinations, vomiting.

Patient Information

  • Advise patient or caregiver to review the patient information leaflet carefully before starting therapy and to read and check for new information each time the medication is refilled.
  • Review dosing schedule with patient.
  • Advise patient with Parkinson disease, or caregiver, that medication is not a cure for Parkinson disease but may help reduce the symptoms of Parkinson disease. Instruct patient to continue to take other medications for Parkinson disease as prescribed by health care provider.
  • Advise patient or caregiver that medication is started at a low dose and gradually increased to achieve max benefit.
  • Advise patient or caregiver that medication can be taken without regard to meals, but to take with food if stomach upset occurs.
  • Advise patient or caregiver that medication should be taken exactly as prescribed and not to stop taking or change the dose unless advised by health care provider.
  • Advise patient or caregiver that if a dose is missed, to skip that dose and take the next dose at the regularly scheduled time. Caution patient never to double the dose to catch up.
  • Advise patient or caregiver that if medication has been temporarily stopped for any reason not to restart without discussing with health care provider. The medication may need to be restarted at a low dose and gradually increased.
  • Instruct patient to avoid alcohol and other CNS depressant medications while taking ropinirole.
  • Advise patient or caregiver that medication may cause postural hypotension with or without symptoms such as dizziness, fainting, nausea, and sweating, especially when therapy is first started or following a dosage increase.
  • Caution patient to get up slowly from a lying or sitting position and to avoid sudden position changes to prevent postural hypotension. Instruct patient to lie or sit down if they experience dizziness, light-headedness, and/or faintness when standing.
  • Advise patient or caregiver that medication may cause hallucinations (unreal visions, sounds, or sensations) and to notify health care provider if noted.
  • Advise patient that drug may cause drowsiness and present the possibility of falling asleep while engaged in activities of daily living, and to use caution while driving or performing other tasks requiring mental alertness until tolerance is determined. Instruct patient to stop driving or participating in other potentially dangerous activities and to notify health care provider if they experience increasing drowsiness or sleepiness, or episodes of falling asleep during activities of daily living.
  • Advise patient or caregiver to report any of the following to health care provider: dizziness, faintness, nausea, or sweating when standing from a sitting or lying position; hallucinations; involuntary body or facial movements; mood or mental changes; persistent or frequent nausea or vomiting; any other unexplained symptom or sign.
  • Instruct patients to notify health care provider if they start or stop smoking while taking ropinirole.

Copyright © 2009 Wolters Kluwer Health.

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