Pronunciation: roe-PIN-i-ROLE HYE-droe-KLOR-ide
Class: Non-ergot dopamine receptor agonist
- Tablets 0.25 mg
- Tablets 0.5 mg
- Tablets 1 mg
- Tablets 2 mg
- Tablets 3 mg
- Tablets 4 mg
- Tablets 5 mg
- Tablets, extended-release 2 mg
- Tablets, extended-release 4 mg
- Tablets, extended-release 8 mg
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.
Mechanism of action as treatment for restless legs syndrome (RLS) is unknown.
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.
Widely distributed; Vd is 7.5 L/kg. Up to 40% protein bound.
Extensively metabolized in liver to inactive metabolites; CYP1A2 is major enzyme involved in metabolism.
Eliminated in urine (less than 10% as unchanged drug). Elimination half-life is approximately 6 h. Cl is 47 L/h.
Special PopulationsRenal 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).
Dosage and AdministrationParkinson 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
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).
- 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.
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 InteractionsCNS 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.
Syncope (12%); orthostatic hypotension (6%); hypertension (5%); palpitation, peripheral ischemia (3%); atrial fibrillation, extrasystole, hypotension, tachycardia (2%); bradycardia, hot flush (at least 1%).
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).
Increased sweating (7%); flushing (3%); night sweats, rash (at least 1%).
Nasopharyngitis (9%); abnormal vision, pharyngitis (6%); rhinitis (4%); eye abnormality (3%); diplopia, nasal congestion, xerophthalmia (2%); pharyngolaryngeal pain (at least 1%).
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%).
UTI (6%); impotence (3%); pyuria, urinary incontinence (2%); erectile dysfunction, hematuria (at least 1%).
Increased alkaline phosphatase (3%); weight decrease (2%); hyperglycemia, increased BUN (at least 1%).
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%).
Upper respiratory tract infection (9%); sinusitis (4%); bronchitis, cough, dyspnea (3%); asthma, lower respiratory tract infection (at least 1%).
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%).
Category C .
Safety and efficacy not established.
Incidence of hallucinations appears to be increased with age.
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).
Use with caution in patients with severe CV disease.
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.
A small number of cases of possible fibrotic complications, including cardiac valvulopathy, interstitial lung disease, pleural effusion, and pleural fibrosis, have been reported.
Can occur during ropinirole therapy.
Postural hypotension may occur, especially during dose escalation.
Impulse control symptoms, including compulsive behavior, such as pathological gambling and hypersexuality, have been reported.
Major psychotic disorders
Major psychotic disorders may be exacerbated.
Patients with Parkinson disease have a higher risk of developing melanoma than the general population.
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.
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.
- 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.
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