Professional Information

Ropinirole Hydrochloride

Pronouncation: (row-PIN-ih-role)
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

Pharmacology

Feedback for Ropinirole Hydrochloride

As a treatment for...	Avg User Ratings [?]
Restless Legs Syndrome	4 comments Rate it!	8.4
Parkinson's Disease	1 comments Rate it!	6.0
Periodic Limb Movement Disorder	Be the first to rate it 0 comments

Compare with other drugs.

Precise mechanism of action as 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) unknown.

Pharmacokinetics

Absorption

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

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 t _½ is about 6 h. Cl is 47 L/h.

Special Populations

Elderly

Cl is reduced 30% in patients older than 65 yr of age.

Cigarette smoking

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

Indications and Usage

Treatment of the signs and symptoms of idiopathic Parkinson disease. Treatment of moderate to severe primary RLS.

Contraindications

Standard considerations.

Dosage and Administration

Parkinson Disease

Individualize by careful titration.

Adults

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

RLS
Adults

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

General Advice

Administer prescribed dose 3 times daily to patients with Parkinson disease.
Administer prescribed dose once daily, 1 to 3 h before bedtime, to patients with RLS.
Administer without regard to meals. Administer with food if GI upset occurs.
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

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

Drug Interactions

CNS depressants (eg, alcohol)

Use with caution because of additive CNS effects.

CYP1A2 inducers (eg, cigarette smoking, rifampin)

May increase metabolic clearance of ropinirole.

CYP1A2 inhibitors (eg, ciprofloxacin, erythromycin, fluvoxamine)

May decrease metabolic clearance of ropinirole.

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

May reduce effectiveness of ropinirole.

Estrogen

May reduce clearance of ropinirole.

Levodopa

Ropinirole mat potentiate dopaminergic side effects of levodopa and may cause or exacerbate pre-existing dyskinesias.

Laboratory Test Interactions

None well documented.

Adverse Reactions

Cardiovascular

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

CNS

Dizziness, somnolence (40%); fatigue (11%); asthenia (6%); confusion, hallucination (5%); hypesthesia (4%); amnesia, malaise, paresthesia, yawning, (3%); hyperkinesis, impaired concentration, vertigo (2%); headache, insomnia (at least 2%); anxiety, depression, hypoesthesia, irritability, migraine, neuralgia, sleep disorder (at least 1%); pathological gambling (post marketing).

Dermatologic

Increased sweating (6%); flushing (3%); night sweats, rash (at least 1%).

EENT

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

GI

Nausea (60%); vomiting (12%); dyspepsia (10%); abdominal pain (6%); diarrhea, dry mouth (5%); anorexia, dyspepsia (4%); flatulence (3%); constipation, gastroenteritis, gastroesophageal reflux disease, stomach discomfort, toothache, viral gastroenteritis (at least 1%).

Genitourinary

UTI (5%); impotence (3%); erectile dysfunction (at least 1%).

Metabolic-Nutritional

Increased alkaline phosphatase (3%); increased BUN (at least 1%).

Musculoskeletal

Arthralgia (4%); extremity pain, muscle cramp, neck pain (3%); back pain (at least 2%); muscle spasms, muscle stiffness, myalgia, osteoarthritis, rigors, tendonitis (at least 1%).

Respiratory

Sinusitis (4%); bronchitis, cough, dyspnea (3%); asthma, upper and/or lower respiratory tract infection (at least 1%).

Miscellaneous

Viral infection (11%); pain (8%); leg edema (7%); dependent edema (6%); chest pain (4%); hyperhidrosis, influenza (3%); peripheral edema (2%); asthenia, 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.

Abrupt withdrawal/discontinuation of therapy

Withdraw ropinirole in Parkinson disease patients gradually over a 7 day period. Reduce frequency of administration from 3 times daily to twice daily for 4 days, then once daily for 3 days. Ropinirole may be discontinued in RLS patients with doses up to 4 mg once daily without tapering.

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 severe cardiovascular disease.

Concurrent levodopa use

When ropinirole is administered as adjunct therapy to levodopa, the dose of levodopa may be decreased as tolerated.

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 patient not to drive and to avoid other potentially hazardous activities.

Fibrotic complications

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

Hallucinations

Can occur during ropinirole therapy.

Hypotension

Postural hypotension may occur, especially during dose escalation.

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 maximum 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, lightheadedness, 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 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 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: persistent or frequent nausea or vomiting; involuntary body or facial movements; mood or mental changes; dizziness, nausea, sweating, or faintness when standing from a sitting or lying position; hallucinations; any other unexplained symptom or sign.
Instruct patient to notify health care provider if they start or stop smoking while taking ropinirole.