Прамипекс

General characteristics. Structure:

Active agent: pramipeksola of dihydrochloride monohydrate of 0,25 mg

Other ingredients: mannitol (Е 421), starch corn, silicon dioxide colloid anhydrous, povidone, magnesium stearate.

Active agent: pramipeksola of dihydrochloride monohydrate of 1 mg

Other ingredients: mannitol (Е 421), starch corn, silicon dioxide colloid anhydrous, povidone, magnesium stearate.

Pharmacological properties:

Pharmacodynamics. Pramipeksol is a dopamine agonist with high selectivity and specificity of rather dopamine receptors of the D2 subtype and has preferential affinity to D3 receptors, differs in total internal activity.
Pramipeksol reduces expressiveness of parkinsonichesky motive disturbances by stimulation of dopamine receptors of a striatum (striate body). Pramipeksol suppresses synthesis, release and the address of dopamine.
The exact mechanism of action of Pramipeks at treatment of a syndrome of uneasy legs is unknown. Though the pathophysiology of a syndrome of uneasy legs is generally unknown, neuropharmacological data indicate involvement of primary dofaminergichesky system.

Pharmacokinetics. Pramipeksol is quickly and completely soaked up after oral administration. Absolute bioavailability makes> 90%. Cmax in a blood plasma register in 1–3 h. Speed of absorption does not decrease at a concomitant use of food, but the general level of absorption decreases. Rather insignificant fluctuations of plasma level at different patients are characteristic of Pramipeksol linear kinetics and, irrespective of a dosage form. The person has a linkng of a pramipeksol with proteins of a blood plasma very low (<20%), and distribution volume — big (400 l). Pramipeksol is metabolized at the person only in insignificant quantity.
Allocation by kidneys of not changed pramipeksol is the most important way of elimination. About 90% of a dose, marked 14C, are allocated with kidneys whereas less than 2% are defined in Calais. The general clearance of a pramipeksol makes about 500 ml/min., and renal — about 400 ml/min. Т½ — of 8 h at young patients to 12 h at elderly people.

Indications to use:

Treatment of symptoms of an idiopathic disease of Parkinson at adults as monotherapy (without levodopa) or in a combination with a levodopa during a disease to late stages when the effect of a levodopa decreases or becomes unstable and arises fluctuation of therapeutic effect (a phenomenon of "inclusion switching off").
The symptomatic treatment of an idiopathic syndrome of uneasy legs from moderated to heavy degree at adults in doses is not higher than 0,75 mg.

Route of administration and doses:

Pill is taken orally, irrespective of meal, washing down with water.
Parkinson's disease. The daily dose is divided into 3 receptions in equal parts.
Initial treatment. As shown below, the dose of drug needs to be raised gradually, from initial 0,375 mg/days each 5–7 days. In cases when patients have no intolerable by-effects, the dose needs to be titrated before achievement of the maximum therapeutic effect.

Scheme of increase in a dose of Pramipeks
Week	Dose, mg	General daily dose, mg
The 1st	3 x 0,125	0,375
The 2nd	3 x 0,25	0,75

In need of further increase in a dose the daily dose should be raised on 0,75 mg every week to maximum which makes 4,5 mg/days.
However it should be noted that the frequency of emergence of drowsiness increases at use of a dose of 1,5 mg/days.
Maintenance therapy. The individual dose fluctuates from 0,375 mg to the maximum 4,5 mg/days. At increase in a dose therapeutic effect noted 1,5 mg since a daily dose. The subsequent dose adjustment should be carried out, considering the clinical answer and emergence of side reactions. During the researches about 5% of patients accepted drug in a dose <1,5 mg. At the progressing Parkinson's disease purpose of a dose> 1,5 mg can be reasonable for patients to whom the levodopa dose decline in a combination therapy with a levodopa is planned. The levodopa dose decline at increase in a dose of Pramipeks is recommended and at a maintenance therapy depending on reaction of the patient (see INTERACTIONS).
Treatment termination. The sudden termination of dofaminergichesky therapy can lead to development of an antipsychotic malignant syndrome. The dose of a pramipeksol should be lowered by 0,75 mg/days to a daily dose of 0,75 mg. After that the dose should be reduced to 0,375 mg (see. Special INSTRUCTIONS).
Dosing for patients with a renal failure. Allocation of a pramipeksol depends on function of kidneys. The following scheme of dosing is offered for initial therapy.
Patients with clearance of creatinine of 50 ml/min. do not need decrease in a daily dose or frequency of dosing.
The patient with clearance of creatinine of 20-50 ml/min. the initial daily dose of Pramipeks is appointed in 2 receptions, since 0,125 mg by 2 times a day (0,25 mg/days). It is not necessary to exceed the maximum daily dose of a pramipeksol of 2,25 mg.
To patients with clearance of creatinine <20 ml/min. appoint Pramipeks's dose in 1 reception, since 0,125 mg/days. It is not necessary to exceed the maximum daily dose of a pramipeksol of 1,5 mg.
At deterioration in function of kidneys against the background of a maintenance therapy the daily dose of Pramipeks is lowered by so many percent on how many the clearance of creatinine decreased. For example, at decrease in clearance of creatinine by 30% Pramipeks's dose is lowered by 30%. It is possible to appoint a daily dose in 2 receptions if the clearance of creatinine is in limits of 20-50 ml/min., and in 1 if clearance of creatinine <20 ml/min.
Dosing for patients with an abnormal liver function. For patients with an abnormal liver function the dose decline is not considered necessary as nearly 90% of the absorbed drug are allocated with kidneys. Potential influence of an abnormal liver function on Pramipeks's pharmacokinetics was not investigated.
Syndrome of uneasy legs. The recommended initial dose of Pramipeks makes 0,125 mg of 1 times a day for 2–3 h to a dream. For patients who need additional reduction of expressiveness of symptoms it is possible to raise a dose each 4–7 days to the maximum 0,75 mg (as shown in the table below):

Scheme of increase in a dose of Pramipeks
Titration stage	Single daily evening dose, mg
1	0,125
2 *	0,25
3 *	0,5
4 *	0,75

* In case of need.
Treatment termination. As the daily dose at treatment of a syndrome of uneasy legs does not exceed 0,75 mg, Pramipeks's use can be stopped without gradual dose decline. Resuming of symptoms of a syndrome of uneasy legs (strengthening of weight of symptoms in comparison with initial level) at 10% of patients after sudden phase-out of a pramipeksol is possible. Such effect is possible for all doses. Dosing for patients with a renal failure. Pramipeks's removal from an organism depends on function of kidneys. For patients with clearance of creatinine of 20 ml/min. there is no need for decrease in a daily dose. Pramipeks's use was not studied at the patients who are on a hemodialysis and patients with heavy degree have renal failures.
Dosing for patients with an abnormal liver function. For patients with an abnormal liver function the dose decline is not considered necessary as nearly 90% of drug are allocated with kidneys.

Features of use:

Pramipeks's appointment is offered to patients with a renal failure in reduced doses according to the section USE.
Hallucinations. Hallucinations — the known side reactions of treatment by dopamine agonists and a levodopa. Patients need to be informed that there can be hallucinations (in most cases visual).
Dyskinesia. At a combination therapy with a levodopa at the progressing Parkinson's disease dyskinesia can develop at the beginning of Pramipeks's titration. In that case the dose of a levodopa should be lowered.
Sudden attack of drowsiness and drowsiness. Use of a pramipeksol is connected with drowsiness and episodes of a sudden attack of drowsiness, especially at patients with Parkinson's disease. It was infrequently reported about a sudden attack of drowsiness during daily activity, in certain cases — without understanding or signs harbingers. In this regard patients should be informed on need to be careful at control of vehicles or work with other mechanisms during treatment by Pramipeks. Patients with drowsiness and/or episodes of a sudden attack of drowsiness should refrain from control of vehicles and work with the equipment. Besides, it is necessary to consider the possibility of a dose decline or reduction of term of treatment. Because of possible additive influence it is necessary to show care if the patient applies other sedative medicines or alcohol in combination with pramipeksoly (see INTERACTIONS, SPECIAL INSTRUCTIONS, SIDE EFFECTS).
Disturbance of control over motivation and compulsive behavior. At patients with Parkinson's disease who were treated by dopamine agonists, signs of a morbid attraction to gamblings, decrease a libido and hyper sexuality are noted. Patients and persons who look after them have to know that at patients symptoms of disorder of control over motivation and compulsive behavior, for example an overeating and a morbid attraction to visit of shops can develop. Under such circumstances it is necessary to consider the possibility of decrease in the dose/termination of administration of drug.
Heart failure. At a serious cardiovascular illness it is necessary to appoint drug with extra care. Monitoring of the ABP, especially in an initiation of treatment, taking into account the general risk of developing of the postural hypotension connected with dofaminergichesky therapy is recommended.
Patients with disturbances of mentality. At patients with frustration of mentality it is necessary to apply dopamine agonists only in case the potential advantage of treatment exceeds risk. It is necessary to avoid simultaneous use of antipsychotic medicines with pramipeksoly.
Antipsychotic malignant syndrome. The symptoms reminding an antipsychotic malignant syndrome were noted after sharp cancellation of dofaminergichesky treatment.
Ophthalmologic inspection. Regular ophthalmologic inspection in case of a vision disorder is recommended.
Augmentation. Treatment of a syndrome of uneasy legs dofaminergichesky drugs can cause augmentation. Augmentation is shown in the form of early emergence of symptoms in the evening (or even in the afternoon), increase in expressiveness of symptoms and distribution of symptoms at upper extremities.
Use during pregnancy and feeding by a breast. Influence on pregnancy at people was not investigated. Прамипекс it is possible to apply during pregnancy only in case the potential advantage exceeds risk for a fruit.
As treatment by Pramipeks suppresses prolactin secretion, reduction of a lactation is possible. Pramipeks's excretion in breast milk is not studied at women therefore drug is not recommended to be used during feeding by a breast. If it is impossible to avoid Pramipeks's use, it is necessary to stop feeding by a breast.
Children. Drug is contraindicated to children.
Ability to influence speed of response at control of vehicles or work with other mechanisms. Прамипекс can exert considerable impact on ability to control of vehicles or work with other mechanisms. Emergence of hallucinations or drowsiness therefore recommend to refrain from control of vehicles or work with other mechanisms is possible.

Side effects:

Side reactions are presented on classes of systems of bodies and for emergence frequency: very often (> 1/10), it is frequent (> 1/100– <1/10), infrequently (> 1/1000– <1/100), is rare (> 1/10 000– <1/1000), is very rare (<1/10 000).
Parkinson's disease. Patients with Parkinson's disease at treatment pramipeksoly in comparison with placebo the most frequent side reactions (> 5%) had a nausea, dyskinesia, arterial hypotension, dizziness, drowsiness, sleeplessness, a lock, hallucinations, a headache and fatigue. Frequency of emergence of drowsiness increases at use in a dose of 1,5 mg (see USE). Dyskinesia was the most frequent side reaction at inclusion in combinations with a levodopa. Arterial hypotension can arise in an initiation of treatment, especially if прамипексол it is titrated too quickly.
Infections and invasions: infrequently — pneumonia.
From mentality: often — a sleep disorder, symptoms of disturbance of control over motivation and compulsive behavior, confusion of consciousness, a hallucination, sleeplessness; infrequently — an overeating, a morbid attraction to visit of shops, a mania, a hyperphagia, hyper sexuality, disturbances a libido, paranoia, a morbid attraction to gamblings, concern.
From a nervous system: very often — dizziness, dyskinesia, drowsiness; often — a headache; infrequently — amnesia, a hyperkinesia, a sudden attack of drowsiness, faints.
From an organ of sight: often — a vision disorder, including a diplopia, an illegibility of sight and deterioration in visual acuity.
From cardiovascular system: often — arterial hypotension; infrequently — heart failure.
From respiratory system: infrequently — an asthma, a hiccups.
From the alimentary system: very often — nausea; often — a lock, vomiting.
From skin and hypodermic cellulose: infrequently — hypersensitivity, an itch, rash.
General disturbances: often — fatigue, peripheral hypostases.
Researches: often — a body degrowth, including a loss of appetite; infrequently — increase in body weight.
Syndrome of uneasy legs. Patients with a syndrome of uneasy legs at treatment pramipeksoly frequent side reactions (> 5%) had a nausea, a headache, dizziness and fatigue.
Infections and invasions: infrequently — pneumonia.
From mentality: often — sleep disorders, sleeplessness; infrequently — symptoms of disturbance of control over motivation and compulsive behavior, for example an overeating, a morbid attraction to visit of shops, hyper sexuality and a morbid attraction to gamblings; confusion of consciousness, mania, hallucinations, hyperphagia, disturbances libido, paranoia, concern.
From a nervous system: often — dizziness, a headache, drowsiness; infrequently — amnesia, dyskinesia, a hyperkinesia, a sudden attack of drowsiness, faints.
From an organ of sight: often — a vision disorder, including a diplopia, an illegibility of sight and deterioration in visual acuity.
From cardiovascular system: infrequently — heart failure, arterial hypotension.
From respiratory system: infrequently — an asthma, a hiccups.
From the alimentary system: very often — nausea; often — a lock, vomiting.
From skin and hypodermic cellulose: infrequently — hypersensitivity, an itch, rash.
General disturbances: often — fatigue; infrequently — peripheral hypostases.
Researches: infrequently — a body degrowth, including a loss of appetite, increase in body weight.

Interaction with other medicines:

Linkng with proteins of a blood plasma. Pramipeksol at the person contacts proteins of a blood plasma very slightly (<20%) and has low biotransformation. Therefore interaction with other drug influencing binding of proteins of a blood plasma or elimination by biotransformation is improbable. As anticholinergics eliminirutsya preferential by metabolism in a liver, interaction is improbable.
Interaction with anticholinergics was not investigated.
There is no pharmacokinetic interaction between selegeliny and a levodopa.
Inhibitors/competitors of an active way of renal elimination. Cimetidinum reduces renal clearance of a pramipeksol approximately by 34% probably by suppression of system of transport of cationic renal canalicular secretion. The drugs suppressing active renal canalicular secretion or элиминирующиеся this way such as Cimetidinum, амантадин, мексилетин, a zidovudine, Cisplatinum, quinine and procaineamide, can interact with pramipeksoly and cause reduction of clearance of a pramipeksol. At simultaneous use of these medicines with Pramipeks it is necessary to consider the possibility of a dose decline of a pramipeksol.
Combination with a levodopa. At increase in a dose of Pramipeks the levodopa dose decline is recommended to patients with Parkinson's disease, and doses of other protivoparkinsonichesky means leave invariable.
Because of possible additive influence it is necessary to be careful if the patient applies other sedative medicines or alcohol in combination with pramipeksoly (see. Special INSTRUCTIONS, SIDE EFFECTS).
Antipsychotic medicines. It is necessary to avoid simultaneous use of antipsychotic medicines with pramipeksoly (see. Special INSTRUCTIONS) if antagonistic effects are possible.

Contraindications:

Hypersensitivity to a pramipeksol or any other component of drug.

Overdose:

Clinical experience of considerable overdose is absent. The expected side effects connected with a pharmakodinamichesky profile of a dopamine agonist include nausea, vomiting, a hyperkinesia, hallucinations, excitement and hypotension. The antidote at overdose by a dopamine agonist is not established. In case of signs of excitement of TsNS can appoint neuroleptics. Treatment of patients with overdose can demand the general supporting actions together with a gastric lavage, in/in administration of liquid, use of absorbent carbon and control of an ECG.

Storage conditions:

In original packaging in the place protected from light at a temperature not above 25 °C.

Issue conditions:

According to the recipe

Packaging:

Tab. of 0,25 mg, No. 10, No. 30.

Tab. of 1 mg, No. 10, No. 30.