Mirapex tablets 0.25mg, No. 30

Symptomatic treatment of idiopathic Parkinson's disease (monotherapy or in combination with levodopa) and idiopathic restless legs syndrome.

Inside, regardless of food intake, with water.
The daily dose is evenly divided into 3 doses.
Doses are calculated based on pramipexole dihydrochloride monohydrate.
Symptomatic treatment of Parkinson's disease :
Initial therapy :
As indicated below, the initial daily dose of 0.375 mg is increased every 5-7 days. To reduce side effects, the dose must be selected gradually until the maximum therapeutic effect is achieved.

If necessary to further increase the daily dose, add 0.75 mg per week to a maximum dose of 4.5 mg per day.
Maintenance therapy : The
individual dose should be in the range of 0.375 mg to 4.5 mg per day. Both in the early and late stages of the disease, the drug was effective, starting with a daily dose of 1.5 mg. At the same time, it is possible that in some patients, doses above 1.5 mg per day may give an additional therapeutic effect, especially in the late stage of the disease, when a reduction in the dose of levodopa is indicated.
Discontinuation of treatment : The
dose of the drug should be reduced by 0.75 mg per day, until the daily dose reaches 0.75 mg. Thereafter, the dose should be reduced by 0.375 mg per day.
Doses for patients receiving concomitant therapy with levodopa:
With simultaneous therapy with levodopa, it is recommended to reduce the dose of levodopa as the dose increases, and also during maintenance therapy with pramipexole. This is to avoid excessive dopaminergic stimulation.
Doses for patients with renal impairment:
For initial therapy: in patients with creatinine clearance above 50 ml / min, a decrease in the daily dose or frequency of administration is not required. With a creatinine clearance of 20-50 ml / min, the initial daily dose of the drug is prescribed in two doses, starting from 0.125 mg 2 times a day (0.25 mg per day). The maximum daily dose of 2.25 mg of pramipexole should not be exceeded. When creatinine clearance is less than 20 ml / min, the daily dose of the drug is prescribed once a day, starting at 0.125 mg. The maximum daily dose of 1.5 mg of pramipexole should not be exceeded.
If during maintenance therapy the renal function decreases, then the daily dose of the drug is reduced by the same percentage by which the creatinine clearance decreases, i.e. if creatinine clearance decreases by 30%, then the daily dose of the drug must be reduced by 30%. The daily dose can be divided into two doses if the creatinine clearance is in the range of 20-50 ml / min, and taken once a day if the creatinine clearance is less than 20 ml / min.
Doses for patients with hepatic impairment : There is no need to reduce the dose in patients with hepatic impairment.
Symptomatic treatment of idiopathic restless legs syndrome :
Initial therapy :
The recommended starting daily dose is 0.125 mg, 2-3 hours before bedtime. If patients require additional symptom relief, the dose can be increased every 4-7 days to a maximum dose of 0.75 mg per day.

Maintenance therapy : The
individual dose should be in the range of 0.125 mg to 0.75 mg per day.
Discontinuation of treatment :
Treatment can be discontinued without gradual dose reduction.
In clinical studies, only 10% of patients showed signs of aggravation of symptoms after abrupt discontinuation of treatment, this effect manifested itself at any dose.
Doses for patients with renal insufficiency :
Excretion of the drug depends on renal function and is directly related to creatinine clearance. Based on pharmacokinetic studies in patients with renal insufficiency, a decrease in the daily dose is not required for patients with creatinine clearance greater than 20 ml / min.
The use of the drug MirapexЃ in patients with restless legs syndrome suffering from renal failure has not been studied.
Doses for patients with hepatic impairment: The
need for dose reduction in patients with hepatic impairment is not considered, since approximately 90% of the absorbed drug is excreted by the kidneys.
Dose for children and adolescents : The
safety and efficacy of MirapexЃ in children and adolescents under the age of 18 has not been established.

1 tablet contains:
active substance: pramipexole dihydrochloride monohydrate 0.25 mg (equivalent to 0.18 mg)
excipients : mannitol - 61.0 mg, corn starch - 39.90 mg, colloidal silicon dioxide - 1.20 mg, povidone - 1.15 mg, magnesium stearate - 1.50 mg

Hypersensitivity to pramipexole or to any component of the drug. Children under 18.
Carefully

Renal failure, decreased blood pressure.

Trade name of the drug:

MirapexЃ

International non-proprietary name:

pramipexole

Dosage form:

pills

Composition:

1 tablet contains:
active substance: pramipexole dihydrochloride monohydrate 0.25 mg or 1.0 mg (equivalent to 0.18 mg or 0.7 mg pramipexole base)
excipients : mannitol - 61.0 mg (121.50 mg), starch corn - 39.90 mg (79.85 mg), colloidal silicon dioxide - 1.20 mg (2.30 mg), povidone -1.15 mg (2.35 mg), magnesium stearate - 1.50 mg (3 , 00 mg).

Description:

Tablets 0.25 mg : white oval tablets with a beveled edge, flat on both sides. On one side of the tablet there is a deep risk, on both sides of which there is a marking 'P7', on the other side of the tablet at risk, on both sides of which there is a marking of the company logo.
Tablets 1 mg : white round tablets with a beveled edge, flat on both sides. On one side of the tablet there is a deep risk, on both sides of which there is a marking 'P9', on the other side of the tablet at risk, on both sides of which there is a marking of the company logo.

Pharmacotherapeutic group:

dopamine receptor agonist.

ATX code:

N04DC05

Pharmacological properties

Pharmacodynamics
Pramipexole is an agonist of dopamine receptors, with high selectivity and specificity binds to dopamine receptors of the D2 subgroup, of which it has the most pronounced affinity for D3 receptors. Reduces the deficit of motor activity in Parkinson's disease by stimulating dopamine receptors in the striatum. Pramipexole inhibits the synthesis, release and metabolism of dopamine. Pramipexole in vitro protects dopamine neurons from degeneration in response to ischemia or methamphetamine neurotoxicity.
The exact mechanism of action of the drug in the treatment of restless legs syndrome is currently not known. Despite the fact that the pathophysiology of restless legs syndrome is not fully understood, there is neuropharmacological evidence of the primary involvement of the dopaminergic system in the process. Studies using positron emission tomography (PET) have shown that mild presynaptic dopaminergic dysfunction in the striatum may be involved in the pathogenesis of restless legs syndrome.
Pramipexole in vitro protects neurons from the neurotoxicity of levodopa. Reduces the secretion of prolactin (dose-dependent).
With long-term use (more than 3 years) of pramipexole in patients with Parkinson's disease, there were no signs of a decrease in effectiveness.
When pramipexole was used in patients with restless legs syndrome for 1 year, the effectiveness of the drug was preserved.

Pharmacokinetics
Pramipexole after oral administration is rapidly and completely absorbed. Absolute bioavailability is more than 90%, and maximum plasma concentrations are observed after 1-3 hours. The absorption rate decreases with food intake, but food intake does not affect the total absorption. Pramipexole is characterized by linear kinetics and relatively small variability in concentration between patients.
Pramipexole binds to proteins to a very small extent (<20%), and has a large volume of distribution (400 liters). It is metabolized to an insignificant extent.
About 90% of the dose is excreted through the kidneys (80% unchanged) and less than 2% is found in the feces. The total clearance of pramipexole is about 500 ml / min, renal clearance is about 400 ml / min. The half-life (T%) ranges from 8 hours in young people and up to 12 hours in older people.

Indications for use

Symptomatic treatment of idiopathic Parkinson's disease (monotherapy or in combination with levodopa) and idiopathic restless legs syndrome.

Contraindications

Hypersensitivity to pramipexole or to any component of the drug. Children under 18.
Carefully

Renal failure, decreased blood pressure.

Pregnancy and lactation

The effect on pregnancy and lactation in humans has not been studied.
The possible effects of pramipexole on reproductive function have been investigated in animal experiments. Pramipexole does not show teratogenicity in rats and rabbits, however, at doses toxic to pregnant females, it was embryotoxic in rats.
During pregnancy, the drug should be prescribed only if the potential benefit to the mother outweighs the potential risk to the fetus.
The elimination of the drug in breast milk has not been studied. Since pramipexole inhibits prolactin secretion, it can be assumed that it also inhibits lactation. Therefore, the drug should not be taken during breastfeeding.

Method of administration and dosage

Inside, regardless of food intake, with water.
The daily dose is evenly divided into 3 doses.
Doses are calculated based on pramipexole dihydrochloride monohydrate.
Symptomatic treatment of Parkinson's disease :
Initial therapy :
As indicated below, the initial daily dose of 0.375 mg is increased every 5-7 days. To reduce side effects, the dose must be selected gradually until the maximum therapeutic effect is achieved.

If necessary to further increase the daily dose, add 0.75 mg per week to a maximum dose of 4.5 mg per day.
Maintenance therapy : The
individual dose should be in the range of 0.375 mg to 4.5 mg per day. Both in the early and late stages of the disease, the drug was effective, starting with a daily dose of 1.5 mg. At the same time, it is possible that in some patients, doses above 1.5 mg per day may give an additional therapeutic effect, especially in the late stage of the disease, when a reduction in the dose of levodopa is indicated.
Discontinuation of treatment : The
dose of the drug should be reduced by 0.75 mg per day, until the daily dose reaches 0.75 mg. Thereafter, the dose should be reduced by 0.375 mg per day.
Doses for patients receiving concomitant therapy with levodopa:
With simultaneous therapy with levodopa, it is recommended to reduce the dose of levodopa as the dose increases, and also during maintenance therapy with pramipexole. This is to avoid excessive dopaminergic stimulation.
Doses for patients with renal impairment:
For initial therapy: in patients with creatinine clearance above 50 ml / min, a decrease in the daily dose or frequency of administration is not required. With a creatinine clearance of 20-50 ml / min, the initial daily dose of the drug is prescribed in two doses, starting from 0.125 mg 2 times a day (0.25 mg per day). The maximum daily dose of 2.25 mg of pramipexole should not be exceeded. When creatinine clearance is less than 20 ml / min, the daily dose of the drug is prescribed once a day, starting at 0.125 mg. The maximum daily dose of 1.5 mg of pramipexole should not be exceeded.
If during maintenance therapy the renal function decreases, then the daily dose of the drug is reduced by the same percentage by which the creatinine clearance decreases, i.e. if creatinine clearance decreases by 30%, then the daily dose of the drug must be reduced by 30%. The daily dose can be divided into two doses if the creatinine clearance is in the range of 20-50 ml / min, and taken once a day if the creatinine clearance is less than 20 ml / min.
Doses for patients with hepatic impairment : There is no need to reduce the dose in patients with hepatic impairment.
Symptomatic treatment of idiopathic restless legs syndrome :
Initial therapy :
The recommended starting daily dose is 0.125 mg, 2-3 hours before bedtime. If patients require additional symptom relief, the dose can be increased every 4-7 days to a maximum dose of 0.75 mg per day.

Maintenance therapy : The
individual dose should be in the range of 0.125 mg to 0.75 mg per day.
Discontinuation of treatment :
Treatment can be discontinued without gradual dose reduction.
In clinical studies, only 10% of patients showed signs of aggravation of symptoms after abrupt discontinuation of treatment, this effect manifested itself at any dose.
Doses for patients with renal insufficiency :
Excretion of the drug depends on renal function and is directly related to creatinine clearance. Based on pharmacokinetic studies in patients with renal insufficiency, a decrease in the daily dose is not required for patients with creatinine clearance greater than 20 ml / min.
The use of the drug MirapexЃ in patients with restless legs syndrome suffering from renal failure has not been studied.
Doses for patients with hepatic impairment: The
need for dose reduction in patients with hepatic impairment is not considered, since approximately 90% of the absorbed drug is excreted by the kidneys.
Dose for children and adolescents : The
safety and efficacy of MirapexЃ in children and adolescents under the age of 18 has not been established.

Side effect

Suspected side effects
When using the drug, the following side effects are expected: abnormal dreams, amnesia, behavioral disturbances (symptoms of impulsive and compulsive actions) such as binge eating, compulsive shopping, hypersexuality and pathological gambling; heart failure, confusion, constipation, delirium, dizziness, dyskinesia, shortness of breath, fatigue, hallucinations, headache, hiccups, hyperkinesia, hyperphagia, decreased blood pressure, impaired secretion of antidiuretic hormone, insomnia, sexual desire disorders, nausea, paranoia, peripheral , pneumonia, itching, rash and other signs of hypersensitivity; anxiety, drowsiness, sudden falling asleep, fainting, visual disturbances, including diplopia, decreased visual acuity and clarity of perception, vomiting,weight loss, including decreased appetite, weight gain.
Based on the analysis of pooled data from placebo-controlled studies, including a total of 1923 patients taking pramipexole and 1354 patients taking placebo, side effects were reported frequently in both groups. 63% of patients taking pramipexole and 52% of patients taking placebo reported at least one adverse drug reaction.
Tables 1 and 2 show the incidence of side effects from placebo-controlled clinical trials for Parkinson's disease and restless legs syndrome. The adverse drug reactions listed in these tables are those observed in 0.1% or more of pramipexole-treated patients, significantly more frequent in pramipexole-treated patients than in the placebo group, or those events that were recognized clinically significant. Most side effects were mild to moderate, usually manifested early in therapy, and most tended to resolve even with continued therapy.
Within the system-organ classes, the following categories are used in terms of the incidence of side effects: very often ( >1/10); often ( > 1/100, <1/10); infrequently ( > 1/1000, <1/100); rarely ( > 1/10000, <1/1000); very rarely <1/10000).
Parkinson's disease, the most common side effects

The most frequently ( > 5%) reported adverse drug reactions in patients with Parkinson's disease, more often with pramipexole than with placebo, were nausea, dyskinesia, decreased blood pressure, dizziness, drowsiness, insomnia, constipation, hallucinations, headache, and fatigue. The incidence of drowsiness is increased with a dose exceeding 1.5 mg of pramipexole salt per day. The most common side effect when combined with levodopa was dyskinesia. A decrease in blood pressure may develop at the beginning of therapy, especially if the dose of pramipexole is increased too quickly.

Overdose

Cases of severe overdose have not been described.
Presumptive symptoms inherent in the pharmacodynamic profile of dopamine receptor agonists : nausea, vomiting, hyperkinesia, hallucinations, agitation and a decrease in blood pressure.
Treatment : there is no established antidote; in case of an overdose, gastric lavage, symptomatic therapy, dynamic observation are recommended.
The effectiveness of hemodialysis has not been established. With signs of CNS excitation, it is possible to prescribe antipsychotics.

Drug interactions

Pramipexole to a small extent (<20%) binds to plasma proteins and undergoes biotransformation. Therefore, interactions with other drugs that affect binding to plasma proteins, or excretion due to biotransformation are unlikely.
Drugs that inhibit the active secretion of cationic drugs through the renal tubules (for example, cimetidine), or which themselves are excreted by active secretion through the renal tubules, can interact with pramipexole, which is reflected in a decrease in the clearance of one or both drugs. In the case of the simultaneous use of such drugs (including amantadine) and pramipexole, it is necessary to pay attention to such signs of excessive dopamine stimulation as dyskinesia, agitation or hallucinations. In certain cases, it is necessary to reduce the dose.
Selegiline and levodopa do not affect the pharmacokinetics of pramipexole. Paramipexole does not affect the overall absorption or elimination of levodopa. Interaction with anticholinergic drugs and amantadine has not been studied. However, interaction with amantadine is possible because drugs have a similar elimination mechanism. Anticholinergics are mainly metabolized, so interactions with pramipexole are unlikely.
With an increase in the dose of pramipexole, a decrease in the dose of levodopa is recommended, while the dose of other antiparkinsonian drugs must be maintained at a constant level.
Due to the possible cumulative effects, patients should be advised to exercise caution when taking other sedative drugs or alcohol in combination with MirapexЃ, as well as while taking drugs that increase the plasma concentration of pramipexole (for example, cimetidine).
Simultaneous administration of pramipexole with antipsychotics should be avoided (for example, if antagonism is expected).

special instructions

Hallucinations and confusion are known side effects in the treatment of dopamine agonists and levodopa.When using the drug MirapexЃ in combination with levodopa in the late stages of the disease, hallucinations were observed more often than with pramipexole monotherapy in patients at an early stage of the disease. Patients should be informed about the possibility of hallucinations (mainly visual), which can affect the ability to drive a car.
Patients and their caregivers should be aware that in connection with the treatment of patients with dopaminergic drugs, signs of abnormal behavior (symptoms of impulsive and compulsive actions), such as a tendency to overeat (hyperphagia), an obsessive desire to shop (pathological shopping), hypersexuality and pathological gambling. In such cases, a decision should be made on dose reduction / gradual discontinuation of treatment.
In patients with psychotic disorders, the appointment of dopamine agonists in combination with pramipexole is possible only after a preliminary assessment of the possible risk-benefit. Concomitant use of pramipexole with antipsychotics should be avoided.
It is recommended to check your eyesight at regular intervals or immediately after prescribing the drug in the presence of such disorders.
Care should be taken if the patient has a severe cardiovascular disease. Due to the risk of orthostatic hypotension during therapy with dopaminergic drugs, it is recommended to control blood pressure, especially at the beginning of treatment.
Patients should be warned about the possible sedative effect of the drug. It has been reported that cases of drowsiness and sudden falling asleep during daily activities (including driving a car or operating complex mechanisms) can occur at any time during treatment, and patients should be informed about this.
Epidemiological studies have shown that patients with Parkinson's disease have a higher risk (2 to about 6 times higher) of developing melanoma than the general population. Whether this increased risk is due to Parkinson's disease or is related to other factors, such as medications used for Parkinson's disease, is not known.
Due to the reasons given above, patients and their caregivers should be informed that during the period of taking pramipexole or other dopaminergic drugs, it is necessary to be attentive to the possible development of melanoma.
Parkinson's disease :
It has been reported that with an abrupt discontinuation of therapy, a symptom complex resembling neuroleptic malignant syndrome was observed.
Increased restless legs syndrome

Reports in the literature suggest that treatment of restless legs syndrome with dopaminergic drugs may increase it.
This increase represented an earlier onset of symptoms in the evening (or even in the afternoon), an increase in this symptomatology and the spread of symptoms to other extremities. However, in a 26-week controlled clinical study specifically devoted to the study of this effect, there was no significant difference in the increase in clinical symptoms between the pramipexole and placebo groups.

Influence on the ability to drive a car and equipment

Patients should be informed about the likelihood of hallucinations (mainly visual) that can affect the ability to drive a car.
ѕри применении препарата возможно развитие седативных эффектов, включа¤ сонливость и засыпание во врем¤ повседневной де¤тельности. ѕоскольку сонливость ¤вл¤етс¤ частым нежелательным ¤влением с потенциально серьЄзными последстви¤ми, пациенты не должны управл¤ть автомобилем или работать с другими сложными механизмами до тех пор, пока они не приобретут достаточного опыта лечени¤ препаратом ћирапексЃ, чтобы оценить вли¤ет ли он отрицательно или нет на их умственную и/или двигательную активность. ?сли во врем¤ лечени¤ пациенты испытывают повышенную сонливость или эпизоды засыпани¤ во врем¤ повседневной де¤тельности (т.е. во врем¤ разговора, еды и т.д.), они должны отказатьс¤ от управлени¤ автомобилем, работы с техникой, и обратитьс¤ к врачу.

‘орма выпуска

Tablets 0.25 mg or 1 mg.
10 tablets in a PA / aluminum foil / PVC blister. 3 blisters with instructions for use in a cardboard box.

Storage conditions

Store at a temperature not exceeding 30 ? C, protected from light and out of reach of children.

Shelf life

3 years. Do not use the drug after the expiration date printed on the package.

Conditions of dispensing from pharmacies

on prescription.