PRAMIPEXOLE KRKA

Posology Pramipexole Krka prolonged-release tablets are a once-a-day oral formulation of pramipexole. 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). Patients already taking Pramipexole Krka tablets may be switched to Pramipexole Krka prolonged-release tablets overnight, at the same daily dose. 1). 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). Missed dose When the intake of a dose is missed, Pramipexole Krka prolonged-release tablets should be taken within 12 hours after the regularly scheduled time.

After 12 hours, the missed dose should be left out and the next dose should be taken on the following day at the next regularly scheduled time. 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). 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. 26 mg Pramipexole Krka prolonged-release tablets every other day. Caution should be exercised and careful assessment of therapeutic response and tolerability should be made before increasing to daily dosing after one week.

25 mg of salt) per day. The treatment of patients with a creatinine clearance below 30 ml/min with Pramipexole Krka prolonged-release tablets is not recommended as no data are available for this patient population. The use of Pramipexole Krka tablets should be considered.

If renal function declines during maintenance therapy, the recommendations given above should be followed. 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 Pramipexole Krka pharmacokinetics has not been investigated. Paediatric population The safety and efficacy of Pramipexole Krka in children below 18 years has not been established.

There is no relevant use of Pramipexole Krka prolonged-release tablets in the paediatric population for the indication of Parkinson’s Disease. Method of administration The tablets should be swallowed whole with water, and must not be chewed, divided or crushed.

The tablets may be taken either with or without food and should be taken each day at about the same time.

Based on the analysis of pooled placebo-controlled trials, comprising a total of 1,778 Parkinson’s disease patients on pramipexole and 1,297 patients on placebo, adverse drug reactions were frequently reported for both groups. 67% of patients on pramipexole and 54% 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).

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. Body System Very common (≥1/10) Common (≥1/100 to <1/10) Uncommon (≥1/1,000 to <1/100) Rare (≥1/10,00 0 to <1/1,000) Not known Infections and infestations pneumonia Endocrine inappropriate disorders 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 somnolenc e, 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 Gastrointesti nal disorders nausea constipation, vomiting Skin and subcutaneou s tissue disorders hypersensitivity, pruritus, rash Reproductiv e system and breast disorders spontaneo us penile erection General disorders and administrati on site conditions fatigue, peripheral oedema dopamine agonist withdrawal syndrome including apathy, anxiety, depression, fatigue, sweating and pain.

Investigatio ns weight decrease including decreased appetite weight increase 1 This side effect has been observed in post-marketing experience. With 95 % certainty, the frequency category is not greater than uncommon, but might be lower.

A precise frequency estimation is not possible as the side effect did not occur in a clinical trial database of 2,762 patients with Parkinson’s Disease treated with pramipexole. 4). Libido disorders Pramipexole may uncommonly be associated with libido disorders (increased or decreased).

4). 6% of all patients receiving dopaminergic or non- dopaminergic treatment had symptoms of an impulse control disorder during the past six months. Manifestations observed include pathological gambling, compulsive shopping, binge eating, and compulsive sexual behaviour (hypersexuality).

Possible independent risk factors for impulse control disorders included dopaminergic treatments and higher doses of dopaminergic treatment, younger age (≤ 65 years), not being married and self-reported family history of gambling behaviours.

Dopamine agonist withdrawal syndrome Non-motor adverse effects may occur when tapering or discontinuing dopamine agonists including pramipexole. 4). Cardiac failure In clinical studies and post-marketing experience cardiac failure has been reported in patients with pramipexole.

85). 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 or search for MHRA Yellow Card in the Google Play or Apple App Store.

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 Pramipexole Krka.

If they occur, the dose of levodopa should be decreased. Dystonia Axial dystonia including antecollis, camptocormia and pleurothotonus (Pisa Syndrome) has occasionally been reported in patients with Parkinson’s disease following initiation or incremental dose increase of pramipexole.

Although dystonia may be a symptom of Parkinson’s disease, the symptoms in these patients have improved after reduction or withdrawal of pramipexole. If dystonia occurs, the dopaminergic medication regimen should be reviewed and an adjustment in the dose of pramipexole considered.

Sudden onset of sleep and somnolence Pramipexole 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 Pramipexole Krka. Patients who have experienced somnolence and/or an episode of sudden sleep onset must refrain from driving or operating machines.

Furthermore a reduction of the dose or termination of therapy may be considered. 8). 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 Pramipexole Krka.

Dose reduction/tapered discontinuation should be considered if such symptoms develop. Mania and delirium Patients should be regularly monitored for the development of mania and delirium. Patients and carers should be made aware that mania and delirium can occur in patients treated with pramipexole.

Dose reduction/tapered discontinuation should be considered if such symptoms develop. Patients with psychotic disorders Patients with psychotic disorders should only be treated with dopamine agonists if the potential benefits outweigh the risks.

5). Ophthalmologic monitoring Ophthalmologic monitoring is recommended at regular intervals or if vision abnormalities occur. Severe cardiovascular disease In case of severe cardiovascular disease, care should be taken. It is recommended to monitor blood pressure, especially at the beginning of treatment, due to the general risk of postural hypotension associated with dopaminergic therapy.

2). 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 pramipexole, 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 pramipexole at the lowest effective dose may be considered.

Remnants in stool Some patients have reported the occurrence of remnants in faeces which may resemble intact Pramipexole Krka prolonged-release tablets. If patients report such an observation, the physician should reassess patient’s response to therapy.

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