ROPILYNZ XL

Oral Use Posology Adults Individual dose titration against efficacy and tolerability is recommended. Ropilynz XL prolonged release tablets should be taken once a day, at a similar time each day. 2). Ropylinz XL prolonged release tablets must be swallowed whole and must not be chewed, crushed or divided.

Initial titration The starting dose of ropinirole prolonged-release tablets is 2 mg once daily for the first week; this should be increased to 4 mg once daily from the second week of treatment. A therapeutic response may be seen at a dose of 4 mg once daily of ropinirole prolonged-release tablets.

Patients who initiate treatment with a dose of 2 mg/day of ropinirole prolonged-release tablets and who experience undesirable effects that they cannot tolerate, may benefit from switching to treatment with ropinirole film-coated tablets (immediate-release) at a lower daily dose, divided into three equal doses.

Therapeutic regimen Patients should be maintained on the lowest dose of ropinirole prolonged- release tablets that achieves symptomatic control. If sufficient symptomatic control is not achieved or maintained at a dose of 4 mg once daily of ropinirole prolonged-release tablets, the daily dose may be increased by 2 mg at weekly or longer intervals up to a dose of 8 mg once daily of ropinirole prolonged-release tablets.

If sufficient symptomatic control is still not achieved or maintained at a dose of 8 mg once daily of ropinirole prolonged-release tablets, the daily dose may be increased by 2 mg to 4 mg at two weekly or longer intervals. The maximum daily dose of ropinirole prolonged-release tablets is 24 mg.

It is recommended that patients are prescribed the minimum number of ropinirole prolonged- release tablets that are necessary to achieve the required dose by utilising the highest available strengths of ropinirole prolonged-release tablets.

If treatment is interrupted for one day or more, re-initiation by dose titration should be considered (see above). When Ropilynz XL prolonged-release tablets are administered as adjunct therapy to levodopa, it may be possible to gradually reduce the levodopa dose, depending on the clinical response.

In clinical trials, the levodopa dose was reduced gradually by approximately 30% in patients receiving ropinirole prolonged-release tablets concurrently. In patients with advanced Parkinson's disease, receiving Ropilynz XL prolonged-release tablets in combination with levodopa, dyskinesias can occur during the initial titration of Ropilynz XL prolonged-release tablets.

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). Switching from ropinirole film-coated (immediate release) tablets to Ropilynz XL prolonged- release tablets Patients may be switched overnight from ropinirole film-coated (immediate- release) tablets to ropinirole prolonged-release tablets.

The dose of ropinirole prolonged-release tablets should be based on the total daily dose of ropinirole film-coated (immediate- release) tablets that the patient was taking. The recommended dose for switching from ropinirole film-coated (immediate-release) tablets to ropinirole prolonged-release tablets are provided in the following table.

5 - 9 8 12 12 15 - 18 16 21 20 24 24 After switching to Ropilynz XL prolonged-release tablets, the dose may be adjusted depending on the therapeutic response (see “Initial titration” and “Therapeutic regimen” above). 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 dose adjustment is necessary in this population.

A study into the use of ropinirole in patients with end stage renal disease (patients on haemodialysis) has shown that a dose adjustment in these patients is required as follows: The recommended initial dose of Ropilynz XL is 2 mg once daily.

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.

Elderly The clearance of ropinirole is decreased by approximately 15% in patients 65 years of age 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.

In patients aged 75 years and above, slower titration during treatment initiation may be considered. Paediatric population Ropilynz XL prolonged-release tablets are not recommended for use in children below 18 years of age due to a lack of data on safety and efficacy.

Adverse events 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. The following adverse events have been reported in either Parkinson's disease clinical trials with ropinirole prolonged-release or film-coated (immediate-release) tablets at doses up to 24 mg/day, or from post- marketing reports: In monotherapy In adjunct therapy Immune system disorders Not known Hypersensitivity reactions (including urticaria, angioedema, rash, pruritus).

Psychiatric disorders Common Hallucinations Confusion Uncommon Psychotic reactions (other than hallucinations) including delirium, delusion, paranoia. ). 4) Aggression* Dopamine dysregulation syndrome Nervous system disorders Very common Somnolence Somnolence** Syncope Dyskinesia*** Common Dizziness (including vertigo), sudden onset of sleep Uncommon Excessive daytime somnolence Vascular disorders Common Postural hypotension, hypotension Uncommon Postural hypotension, hypotension Respiratory, thoracic and mediastinal disorders Uncommon Hiccups Gastrointestinal disorders Very common Nausea Nausea**** Common Constipation, heartburn 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 and administration site conditions Common Oedema peripheral Leg oedema Not known Dopamine agonist withdrawal syndrome (including apathy, anxiety, depression, fatigue, sweating and pain)**** *Aggression has been associated with psychotic reactions as well as compulsive symptoms.

** Somnolence has been reported very commonly in the adjunct therapy immediate- release clinical trials, and commonly in the adjunct therapy prolonged-release clinical trials. *** In patients with advanced Parkinson's disease, dyskinesias can occur during the initial titration of ropinirole.

2). ****Nausea has been reported very commonly in the adjunct therapy immediate- release clinical trials, and commonly in the adjunct therapy prolonged-release clinical trials. 4 ). 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 or search for MHRA Yellow Card in the Google Play or Apple App Store).

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. 8). 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 sleep onset must refrain from driving or operating machines. Furthermore, a reduction of dose 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 Ropilynz XL tablets.

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.

Therefore, it is recommended to taper treatment. 2). Rapid gastrointestinal transit Ropilynz XL tablets are designed to release the active substance over a 24 hour period. If rapid gastrointestinal transit occurs, there may be risk of incomplete release of the active substance and of the active substance residue being passed in the stool.

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 an adverse reaction of treatment with dopamine agonists and levodopa.

Patients should be informed that hallucinations can occur.

Excipients:

Ropilynz XL 2mg contains lactose. Patients with rare hereditary problems of galactose intolerance, the total lactase deficiency or glucose-galactose malabsorption should not take this medicinal product. This medicinal product contains less than 1 mmol sodium (23 mg) per prolonged-release tablet, that is to say essentially 'sodium-free'.

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