Sifrol

Posology Parkinson’s disease The daily dose is administered in equally divided doses 3 times a day. 375 mg of salt) per day and then increased every 5-7 days. Providing patients do not experience intolerable undesirable effects, the dose should be titrated to achieve a maximal therapeutic effect.

5 mg of salt) per day. 8). 5 mg of salt) per day. 5 mg of salt). Further dose adjustments should be done based on the clinical response and the occurrence of adverse reactions. 5 mg of salt). 5 mg of salt) per day can be useful in patients where a reduction of the levodopa therapy is intended.

5). Treatment discontinuation Abrupt discontinuation of dopaminergic therapy can lead to the development of a neuroleptic malignant syndrome or a dopamine agonist withdrawal syndrome. 75 mg of salt). 4). 4). 4 Renal impairment The elimination of pramipexole is dependent on renal function.

The following dose schedule is suggested for initiation of therapy:

Patients with a creatinine clearance above 50 mL/min require no reduction in daily dose or dosing frequency. 25 mg of salt daily). 25 mg of salt) should not be exceeded. 125 mg of salt) daily. 5 mg of salt) should not be exceeded. e. if creatinine clearance declines by 30%, then the SIFROL daily dose should be reduced by 30%.

The daily dose can be administered in two divided doses if creatinine clearance is between 20 and 50 mL/min and as a single daily dose if creatinine clearance is less than 20 mL/min. Hepatic impairment Dose adjustment in patients with hepatic failure is probably not necessary, as approx.

90% of absorbed active substance is excreted through the kidneys. However, the potential influence of hepatic insufficiency on SIFROL pharmacokinetics has not been investigated. Paediatric population The safety and efficacy of SIFROL in children below 18 years has not been established.

There is no relevant use of SIFROL in the paediatric population for the indication of Parkinson’s Disease. 125 mg of salt) taken once daily 2-3 hours before bedtime. 75 mg of salt) per day (as shown in the table below). The lowest effective dose should be used (see section

Based on the analysis of pooled placebo-controlled trials, comprising a total of 1 923 patients on pramipexole and 1 354 patients on placebo, adverse drug reactions were frequently reported for both groups. 63% of patients on pramipexole and 52% of patients on placebo reported at least one adverse drug reaction.

The majority of adverse drug reactions usually start early in therapy and most tend to disappear even as therapy is continued. Within the system organ classes, adverse reactions are listed under headings of frequency (number of patients expected to experience the reaction), using the following categories: 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).

Parkinson’s disease, most common adverse reactions The most commonly (≥ 5%) reported adverse drug reactions in patients with Parkinson’s disease more frequent with pramipexole treatment than with placebo were nausea, dyskinesia, hypotension, dizziness, somnolence, insomnia, constipation, hallucination, headache and fatigue.

2). A more frequent adverse drug reaction in combination with levodopa was dyskinesia. Hypotension may occur at the beginning of treatment, especially if pramipexole is titrated too fast. 9 Table 1: Parkinson’s disease Body System 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) Not known Infections and infestations pneumonia Endocrine disorders inappropriate antidiuretic hormone secretion1 Psychiatric disorders insomnia hallucinations abnormal dreams confusion behavioural symptoms of impulse control disorders and compulsions compulsive shopping pathological gambling restlessness hypersexuality delusion libido disorder paranoia delirium binge eating1 hyperphagia1 mania Nervous system disorders somnolence dizziness dyskinesia headache sudden onset of sleep amnesia hyperkinesia syncope Eye disorders visual impairment including diplopia vision blurred visual acuity reduced Cardiac disorders cardiac failure1 Vascular disorders hypotension Respiratory, thoracic, and mediastinal disorders dyspnoea hiccups Gastrointestinal disorders nausea constipation vomiting Skin and subcutaneous tissue disorders hypersensitivity pruritus rash Reproductive system and breast disorders spontaneous penile erection General disorders and administration site conditions fatigue peripheral oedema dopamine agonist withdrawal syndrome including apathy, anxiety, 10 depression, fatigue, sweating and pain.

4 Restless legs augmentation syndrome). 75 * if needed Patient’s response should be evaluated after 3 months treatment and the need for treatment continuation should be reconsidered. If treatment is interrupted for more than a few days it should be re-initiated by dose titration carried out as above.

75 mg of salt) SIFROL can be discontinued without tapering off. In a 26 week placebo controlled trial, rebound of RLS symptoms (worsening of symptom severity as compared to baseline) was 5 observed in 10% of patients (14 out of 135) after abrupt discontinuation of treatment.

This effect was found to be similar across all doses. Renal impairment The elimination of pramipexole is dependent on renal function. Patients with a creatinine clearance above 20 mL/min require no reduction in daily dose. The use of SIFROL has not been studied in haemodialysis patients, or in patients with severe renal impairment.

Hepatic impairment Dose adjustment in patients with hepatic failure is not required, as approx. 90% of absorbed active substance is excreted through the kidneys. Paediatric population SIFROL is not recommended for use in children and adolescents below 18 years due to a lack of data on safety and efficacy.

Tourette Disorder Paediatric population SIFROL is not recommended for use in children and adolescents below 18 years since the efficacy and safety has not been established in this population. 1). Method of administration The tablets should be taken orally, swallowed with water, and can be taken either with or without food.

1. 2. Hallucinations Hallucinations are known as a side effect of treatment with dopamine agonists and levodopa. Patients should be informed that (mostly visual) hallucinations can occur. Dyskinesia In advanced Parkinson’s disease, in combination treatment with levodopa, dyskinesia can occur during the initial titration of SIFROL.

1.