ROPINIROLE

Posology Parkinson’s disease Adults Individual dose titration of ropinirole against efficacy and tolerability is recommended. Ropinirole should be taken three times a day, preferably with meals to improve gastrointestinal tolerance.

25 mg ropinirole three times daily for 1 week. 5 to 3 mg/day) may be given. A therapeutic response may be seen between 3 and 9 mg/day of ropinirole. If sufficient symptomatic control is not achieved, or maintained after the initial titration as described above, the dose of ropinirole may be increased up to 24 mg/day.

Doses of ropinirole above 24 mg/day have not been studied. If treatment is interrupted for one day or more re-initiation by dose titration should be considered (see above). When ropinirole is administered as adjunct therapy to levodopa, the concurrent dose of levodopa may be reduced gradually according to the symptomatic response.

In clinical trials, the levodopa dose was reduced gradually by around 20% in patients treated with ropinirole as adjunct therapy. In patients with advanced Parkinson's disease receiving ropinirole in combination with levodopa, dyskinesia can occur during the initial titration of ropinirole.

8). When switching treatment from another dopamine agonist to ropinirole, the marketing authorisation holder’s guidance on discontinuation should be followed before initiating ropinirole. 4). For doses not realisable/practicable with this medicinal product other strengths of this medicinal product are available Restless Legs Syndrome Adults Individual dose titration against efficacy and tolerability is recommended.

Ropinirole should be taken just before bedtime; however the dose can be taken up to 3 hours before retiring. Ropinirole may be taken with food, to improve gastrointestinal tolerance. 25 mg once daily (administered as above) for 2 days.

5 mg once daily for the remainder of week 1. Therapeutic regimen (week 2 onwards) Following treatment initiation, the daily dose should be increased until optimal therapeutic response is achieved. The average dose in clinical trials, in patients with moderate to severe Restless Legs Syndrome, was 2 mg once a day.

The dose may be increased to 1 mg once a day at week 2. 5 mg per week over the next two weeks to a dose of 2 mg once a day. In some patients, to achieve optimal improvement, the dose may be increased gradually up to a maximum of 4 mg once a day.

5 mg each week to 3 mg once a day and then by 1 mg up to the maximum recommended dose of 4 mg once a day as shown in the following table. Doses above 4 mg once daily have not been investigated in Restless Legs Syndrome patients. 0 * To achieve optimal improvement in some patients.

1). Patient response should be evaluated after 12 weeks treatment and the need for treatment continuation reconsidered. If treatment is interrupted for more than a few days it should be re-initiated by dose titration as noted above. General information for all therapeutic indications Renal impairment In patients with mild to moderate renal impairment (creatinine clearance between 30 and 50 ml/min) no change in the clearance of ropinirole was observed, indicating that no dosage adjustment is necessary in this population.

25 mg three times a day. Further dose escalations should be based on tolerability and efficacy. The recommended maximum dose is 18 mg/day in patients receiving regular haemodialysis. 2). The use of ropinirole in patients with severe renal impairment (creatinine clearance less than 30 ml/min) without regular haemodialysis has not been studied.

25 mg once daily. Further dose escalations should be based on tolerability and efficacy. The recommended maximum dose of ropinirole is 3 mg/day in patients receiving regular haemodialysis. 2). The use of ropinirole in patients with severe renal impairment (creatinine clearance less than 30 ml/min) without regular haemodialysis has not been studied.

Elderly The clearance of ropinirole is decreased by approximately 15% in patients aged 65 years or above. Although a dose adjustment is not required, ropinirole dose should be individually titrated, with careful monitoring of tolerability, to the optimal clinical response.

Paediatric population Ropinirole is not recommended for use in children below 18 years of age due to a lack of data on […]

Undesirable effects reported are listed below by system organ class and frequency. Frequencies are defined as: very common (≥1/10), common (≥1/100 to <1/10), uncommon (≥1/1,000 to <1/100), rare (≥1/10,000 to <1/1,000), very rare (<1/10,000), not known (frequency cannot be estimated from the available data).

Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness. Use of ropinirole in Parkinson’s disease Undesirable effects are listed below by system organ class and frequency. It is noted if these undesirable effects were reported in clinical trials as monotherapy or adjunct therapy to levodopa.

4) Nervous system disorders Somnolence Monotherapy: Syncope Adjunct therapy: Dyskinesia3 Dizziness (including vertigo) Sudden onset of sleep, excessive daytime somnolence4 Vascular disorders Postural hypotension, hypotension5 Respiratory, thoracic and mediastinal disorders Hiccups Gastro- intestinal disorders Nausea Heartburn Monotherapy: Vomiting, abdominal pain Hepatobiliary disorders Hepatic reactions, mainly increased liver enzymes Reproductive system and breast disorders Spontaneous penile erection General disorders and administration site conditions Monotherapy: Oedema peripheral (including leg oedema) Dopamine agonist withdrawal syndrome (including apathy, anxiety, depression, fatigue, sweating and pain)6 1 Aggression has been associated with psychotic reactions as well as compulsive symptoms.

4). 3 In patients with advanced Parkinson’s disease, dyskinesia can occur during the initial titration of ropinirole. 2). 4 Ropinirole is associated with somnolence and has been associated uncommonly with excessive daytime somnolence and sudden sleep onset episodes.

5 Postural hypotension or hypotension is rarely severe. 4). Use of ropinirole in Restless Legs Syndrome In Restless Legs Syndrome clinical trials the most common adverse drug reaction was nausea (approximately 30% of patients). Undesirable effects were normally mild to moderate and experienced at the start of therapy or on increase of dose and few patients withdrew from the clinical studies due to undesirable effects.

0% above the placebo rate or those reported uncommonly but known to be associated with ropinirole. Adverse drug reactions reported in 12-week Restless Legs Syndrome clinical trials (ropinirole n=309, placebo n=307). 4) Post marketing reports FrequencySystem Organ Class Uncommon (≥1/1,000 to <1/100) Very rare (<1/10,000) Not known Immune system disorders Hypersensitivity reactions (including urticaria, angioedema, rash, pruritus).

Psychiatric disorders Psychic reactions (other than hallucinations) including delirium, delusion and paranoia, dopamine dysregulation syndrome, aggression* Nervous system disorders Excessive daytime somnolence, sudden sleep onset episodes Vascular disorders Postural hypotension or hypotension, which are rarely severe Respiratory, thoracic and mediastinal disorders Hiccups Hepatobiliary disorders hepatic reactions, mainly increase of liver enzymes Reproductive system and breast disorders Spontaneous penile erection General disorders and administration site conditions Dopamine agonist withdrawal syndrome including apathy, anxiety, depression, fatigue, sweating and pain *Aggression has been associated with psychotic reactions as well as compulsive symptoms.

4). 4). Management of undesirable effects Dose reduction should be considered if patients experience significant undesirable effects. If the undesirable effect abates, gradual up-titration can be re-instituted. Anti-nausea medicinal products that are not centrally active dopamine antagonists, such as domperidone, may be used, if required.

Lecithin (soya) may cause very rarely allergic reactions. Reporting of suspected adverse […]

g. caused by renal failure, iron deficiency anaemia or pregnancy). Augmentation (worsening of Restless Legs Syndrome) Paradoxical worsening of Restless Legs Syndrome symptoms described as augmentation (either earlier onset,increased intensity,or spread of symptoms to previously unaffected limbs), or early morning rebound (reoccurrence of symptoms in the early morning hours) have been observed during treatment with ropinirole.

8). 8). However, in Restless Legs Syndrome, this phenomenon is very rare. Nevertheless patients must be informed of this phenomenon and advised to exercise caution while driving or operating machines during treatment with ropinirole. Patients who have experienced somnolence and/or an episode of sudden sleep onset must refrain from driving or operating machines.

A reduction of dosage or termination of therapy may be considered. Psychiatric or psychotic disorders Patients with major psychiatric or psychotic disorders, or a history of these disorders, should only be treated with dopamine agonists if the potential benefits outweigh the risks.

Impulse control disorders Patients should be regularly monitored for the development of impulse control disorders. Patients and carers should be made aware that behavioural symptoms of impulse control disorders including pathological gambling, increased libido, hypersexuality, compulsive spending or buying, binge eating and compulsive eating can occur in patients treated with dopamine agonists including Ropinirole .

Dose reduction/tapered discontinuation should be considered if such symptoms develop. Mania Patients should be regularly monitored for the development of mania. Patients and carers should be made aware that symptoms of mania can occur with or without the symptoms of impulse control disorders in patients treated with ropinirole.

Dose reduction/tapered discontinuation should be considered if such symptoms develop. Neuroleptic malignant syndrome Symptoms suggestive of neuroleptic malignant syndrome have been reported with abrupt withdrawal of dopaminergic therapy.

2). Hypotension Due to the risk of hypotension, blood pressure monitoring is recommended, particularly at the start of treatment, in patients with severe cardiovascular disease (in particular coronary insufficiency). 8). 2). Limited data suggests that patients with impulse control disorders and those receiving high daily dose and/or high cumulative doses of dopamine agonists may be at higher risk for developing DAWS.

Withdrawal symptoms may include apathy, anxiety, depression, fatigue, sweating and pain and do not respond to levodopa. Prior to tapering off and discontinuing ropinirole, patients should be informed about potential withdrawal symptoms.

Patients should be closely monitored during tapering and discontinuation. In case of severe and/or persistent withdrawal symptoms, temporary re-administration of ropinirole at the lowest effective dose may be considered. Hallucinations Hallucinations are known as a side effect of treatment with dopamine agonists and levodopa.

Patients should be informed that hallucinations can occur. Excipients Lactose Patients with rare hereditary problems of galactose intolerance, total lactase deficiency or glucose-galactose malabsorption should not take this medicine.

Sodium This medicinal product contains less than 1 mmol sodium (23 mg) per film-coated tablet, that is to say essentially ‘sodium-free’.

1. Severe renal impairment (creatinine clearance <30 ml/min) without regular haemodialysis. Hepatic impairment.