Ropinirole

Oral
Parkinson's disease
Adult: Alone or as adjunct to reduce the on-off fluctuations in levodopa response: Conventional tab: Initially, 0.25 mg tid, increased in increments of 0.75 mg daily at weekly intervals for the 1st 4 weeks according to response and tolerability. If needed, dose may then be increased by 1.5 mg daily at weekly intervals up to 9 mg daily dose, then by increments of up to 3 mg daily at weekly intervals for the following weeks. Prolonged-release tab: Initially, 2 mg once daily for 1 week, then 4 mg once daily from the 2nd week. If control is insufficient, increase daily dose by 2 mg at intervals of at least 1 week according to response, up to a dose of 8 mg once daily; if needed, increase further by 2-4 mg at intervals of at least 2 weeks. Maintain at lowest effective dose. Max: 24 mg daily. Switching from conventional to prolonged-release tab: May initiate dose of prolonged-release tab based on the total daily dose of the conventional tab (refer to detailed product guideline for specific dosing).
Renal impairment: Patient with ESRD on haemodialysis: As conventional tab: 0.25 mg tid. As prolonged-release tab: 2 mg once daily. All doses may be increased according to efficacy and tolerability. Max: 18 mg daily.

Oral
Restless leg syndrome
Adult: In moderate to severe cases: As conventional tab: Week 1: Initially, 0.25 mg for 2 days; if tolerated, dose may be increased to 0.5 mg once daily for the rest of the week. Week 2 onwards: 1 mg once daily for 7 days, may be increased by 0.5 mg at weekly intervals up to a dose of 3 mg once daily, followed by a final increase to Max of 4 mg once daily on week 7. Dose titrations must be based on individual response and tolerability. All doses are to be given 1-3 hours before bedtime.
Renal impairment: Patient with ESRD on haemodialysis: As conventional tab: Initially, 0.25 mg once daily, may be increased according to efficacy and tolerability. Max: 3 mg daily.

Special Populations: Patient initiated on or withdrawn from concomitant use with CYP1A2 inhibitors or inducers (including cigarette smoking), or estrogen during treatment with ropinirole: Dose adjustment may be required.

Ropinirole: May be taken with or without food. May be taken w/ meals to reduce occurrence of nausea. Swallow whole, do not chew/crush/divide.

Patient with pre-existing dyskinesias, significant CV disease, predisposition to hypotension, cerebrovascular disease. Smokers. Avoid abrupt withdrawal. ESRD (undergoing dialysis) and hepatic impairment. Pregnancy and lactation. Patient receiving estrogen or CYP1A2 inhibitors or inducers. Not recommended for patient with severe renal impairment (CrCl <30 mL/min) without regular dialysis. Avoid use in patient with major psychotic disorder. Patient Counselling This drug may cause excessive daytime somnolence or sudden onset of sleep, if affected, do not drive or operate machinery. Monitoring Parameters Monitor blood pressure periodically; daytime alertness, CNS depression, fall risk, and behaviour changes. Perform periodic skin examinations.

Significant: Paradoxical worsening of RLS symptoms (augmentation or early morning rebound), impulse control disorders (e.g. pathological gambling, hypersexuality, compulsive buying, binge eating), dyskinesias, psychotic effects (e.g. hallucinations, paranoid ideation, delusions, confusion, psychotic-like behaviour, mania, disorientation, aggressiveness, agitation, delirium), somnolence and episodes of sudden sleep onset, orthostatic hypotension or hypotension; syncope, sometimes associated with bradycardia; fibrotic complications (e.g. pleural effusion, pleural fibrosis, interstitial lung disease, cardiac valvulopathy), neuroleptic malignant syndrome (abrupt withdrawal or rapid dose reduction), dopamine agonist withdrawal syndrome. Ear and labyrinth disorders: Vertigo. Gastrointestinal disorders: Nausea, vomiting, constipation, abdominal pain, heartburn, dyspepsia. General disorders and administration site conditions: Peripheral oedema, fatigue, pain. Immune system disorders: Hypersensitivity reaction (e.g. urticaria, angioedema, rash, pruritus). Infections and infestations: Viral infection. Injury, poisoning and procedural complications: Fall. Investigations: Increased liver enzymes. Nervous system disorders: Dizziness, headache. Vascular disorders: Hypertension.

Symptoms: Nausea, dizziness, hallucinations, hyperhidrosis, claustrophobia, chorea, palpitations, asthenia, nightmares; fatigue, vomiting, dyskinesia, agitation, somnolence, confusional state, chest pain, syncope, vasovagal syncope, and hypotension. Management: Symptomatic and supportive treatment. Maintain vital signs if necessary. May administer dopamine antagonists (e.g. neuroleptics, metoclopramide).

Increased plasma concentration with CYP1A2 inhibitors (e.g. ciprofloxacin, enoxacin, fluvoxamine) and hormone replacement therapy (e.g. estrogen). May diminish therapeutic efficacy with neuroleptics (e.g. phenothiazines, butyrophenones, thioxanthenes) and other centrally active dopamine antagonists (e.g. sulpiride, metoclopramide). May result in INR imbalance in concomitant use with vitamin K antagonists. Concomitant use with CNS depressants may enhance the sedative effect of ropinirole.

May enhance sedative effect with alcohol. Decreased rate of absorption with high fat meals.

Ropinirole is a non-ergot derivative dopamine receptor agonist that possesses a full intrinsic activity at the D₂ and D₃ dopamine receptor subtypes, binding with higher affinity to D₃ than to D₂ receptor. Its exact mechanism in the treatment of Parkinson's disease and restless legs syndrome (RLS) has not been fully elucidated, but it is believed to directly stimulate the postsynaptic dopamine receptors in the corpus striatum of the brain.
Absorption: Rapidly absorbed from the gastrointestinal tract (immediate release). Decreased rate of absorption with high fat meals. Bioavailability: Approx 50% (range: 36-57%). Time to peak plasma concentration: Approx 1-2 hours (immediate release); 6-10 hours (prolonged-release).
Distribution: Widely distributed throughout the body. Volume of distribution: 7.5 L/kg. Plasma protein binding: 10-40%.
Metabolism: Extensively metabolised in the liver by the CYP1A2 isoenzyme via N-despropylation and hydroxylation into inactive metabolites. Undergoes first-pass effect.
Excretion: Via urine (<10% as unchanged drug, 60% as metabolites). Elimination half-life: Approx 6 hours.

Oral: Store between 20-25°C. Protect from light.

Antiparkinsonian Drugs

N04BC04 - ropinirole ; Belongs to the class of dopamine agonist. Used in the management of Parkinson's disease.