ROPINIROLE

Oral use. Adults Individual dose titration against efficacy and tolerability is recommended. Parkinson’s disease Ropinirole should be taken three times daily, preferably with meals to improve gastrointestinal tolerance. 25 mg three times daily for one week.

5 to 3 mg/day) of ropinirole 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, dyskinesias can occur during the initial titration of ropinirole.

8). When switching treatment from another dopamine agonist to ropinirole, the marketing authorisation holders guidance on discontinuation should be followed before initiating ropinirole therapy. 4). Restless Legs Syndrome 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. 25mg 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 Table 1.

Doses above 4 mg once daily have not been investigated in Restless Legs Syndrome patients. 5 3 4 * 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 carried out as above. General information for the indications Parkinson’s disease and Restless Legs Syndrome Children and adolescents Ropinirole is not recommended for the use in children and adolescents below 18 years of age due to a lack of data on safety and efficacy.

Elderly patients 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.

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.

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 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). 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).

8 Undesirable effect 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 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.

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.

Hallucinations were reported uncommonly in the open label long-term studies. Paradoxical worsening of Restless Legs Syndrome symptoms occurring with earlier onset (augmentation), and reoccurrence of symptoms in the early morning hours (early morning rebound), may be observed during treatment with ropinirole.

Use of ropinirole in Parkinson’s disease Ropinirole is also indicated for the treatment of Parkinson's disease. Undesirable effects reported 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.

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 (cannot be estimated from the available data). Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness.

Immune system disorders Not known:

Hypersensitivity reactions (including urticaria, angioedema, rash, pruritus). Psychiatric disorders Common: hallucinations. Uncommon: psychotic reactions (other than hallucinations) including delirium, delusion and paranoia. ). * Aggression has been associated with psychotic reactions as well as compulsive symptoms.

).

Use in adjunct therapy studies:

Common: confusion. Nervous system disorders Very common: somnolence Common: dizziness (including vertigo). Uncommon: sudden onset of sleep, excessive daytime somnolence. Ropinirole is associated with somnolence and has been associated uncommonly with excessive daytime somnolence and sudden sleep onset episodes.

Use in monotherapy studies:

Very common: syncope.

Use in adjunct therapy studies:

Very common: dyskinesia. In patients with advanced Parkinson’s disease, dyskinesias can occur during the initial titration of ropinirole. 2). Vascular disorders Uncommon: postural hypotension, hypotension. postural hypotension or hypotension is rarely severe.

Respiratory, thoracic and mediastinal disorders Uncommon: hiccups Gastrointestinal disorders Very common: nausea. Common: heartburn.

Use in monotherapy studies:

Common: vomiting, abdominal pain. Hepatobiliary disorders Not known: hepatic reactions, mainly increased liver enzymes. Reproductive system and breast disorders Not known: spontaneous penile erection General disorders Use in monotherapy studies: Common: Oedema peripheral (including leg oedema).

Not known:

Dopamine agonist withdrawal syndrome (including apathy, anxiety, depression, fatigue, sweating and pain). 4). Reporting of suspected adverse reactions Reporting suspected adverse reactions after authorisation of the medicinal product is important.

It allows continued monitoring of the benefit/risk balance of the medicinal product. uk/yellowcard.

Somnolence and episodes of sudden sleep onset Ropinirole has been associated with somnolence and episodes of sudden sleep onset, particularly in patients with Parkinson's disease. Sudden onset of sleep during daily activities, in some cases, without awareness or warning signs, has been reported uncommonly.

Patients must be informed of this 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 onset sleep 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 the treatment, in patients with severe cardiovascular disease (in particular coronary insufficiency). g. caused by renal failure, iron deficiency anaemia or pregnancy).

During treatment with ropinirole, paradoxical worsening of Restless Legs Syndrome symptoms occurring with earlier onset (augmentation), and reoccurrence of symptoms in the early morning hours (early morning rebound), may be observed.

If this occurs, treatment should be reviewed and dosage adjustment or discontinuation of treatment may be considered. 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 This medicinal product contains lactose. Patients with rare hereditary problems of galactose intolerance, total lactase deficiency or glucose-galactose malabsorption should not take this medicine.

Sodium This medicine contains less than 1 mmol sodium (23 mg) per tablet, that is to say essentially “sodium free”.

Hypersensitivity to ropinirole or to any of the excipients. - Severe renal failure (creatinine clearance < 30 ml/min) and hepatic impairment.