Mirapex, 0.25 mg, 30 pcs.

Active substance:

pramipexole dihydrochloride monohydrate 0.25 mg;

Excipients: 

mannitol; 

corn starch; 

silicon dioxide colloidal; 

povidone;

magnesium stearate.

Mirapex - dopaminergic, antiparkinsonian.

Pharmacodynamics

Pramipexole is an agonist of dopamine receptors, with high selectivity and specificity binds to dopamine receptors of the subgroup D ₂ , of which it has the most pronounced affinity for D ₃ receptors. Reduces motor deficiency in Parkinson's disease by stimulating dopamine receptors in the striatum. 

Pramipexole inhibits dopamine synthesis, release, and metabolism. 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 has not been fully studied, there is neuropharmacological information about the primary involvement of the dopaminergic system in the process. 

Studies performed using positron emission tomography (PET) have shown that moderate 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 prolonged use (more than 3 years) of pramipexole in patients with Parkinson's disease, there were no signs of decreased effectiveness.

When using pramipexole in patients with restless legs syndrome for 1 year, the effectiveness of the drug remained.

Pharmacokinetics

Pramipexole after oral administration is rapidly and completely absorbed. Absolute bioavailability is more than 90%, and C _max  in plasma is observed after 1-3 hours. The absorption rate decreases with food intake, however, food intake does not affect the total absorption volume. 

Pramipexole is characterized by linear kinetics and a relatively small concentration variability between patients.

Pramipexole binds to proteins to a very small extent (d (400 L). It is slightly metabolized. About 90% of the dose is excreted through the kidneys (80% unchanged) and less than 2% is found in feces. 

The total clearance of pramipexole is about 500 ml / min, the renal clearance is about 400 ml / min. T _1/2  ranges from 8 hours in young and up to 12 hours in older people.

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

• Hypersensitivity to pramipexole or to any component of the drug;
• children's age (up to 18 years).

Precautions: renal failure, lowering blood pressure.

From the side of the central nervous system and peripheral nervous system: drowsiness, dyskinesia, hallucinations; in some cases - insomnia. With a rapid reduction in the dose of pramipexole, as well as with a sharp withdrawal of the drug, malignant antipsychotic syndrome was observed. 

From the digestive system: nausea, constipation.

From the cardiovascular system: in some cases, at the beginning of treatment - arterial hypotension (especially with a gradual increase in dose for too short a time).

Other: in some cases, peripheral edema.

With the simultaneous use of Mirapex and levodopa, dyskinesia may develop (in such cases, the dose of levodopa should be reduced).
There is no pharmacokinetic interaction between pramipexole and selegiline.

With simultaneous use with cimetidine, an increase in the concentration of pramipexole in blood plasma is noted. 

Other drugs that are secreted by the organic cation transport system in the kidneys can also increase plasma pramipexole concentrations.

Inside, regardless of the meal, washed down with water.

The daily dose is evenly divided into 3 doses.

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, further increase the daily dose, add 0.75 mg per week to a maximum dose of 4.5 mg / day.

Maintenance therapy An individual dose should be in the range from 0.375 mg to 4.5 mg / 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 higher than 1.5 mg / day can give an additional therapeutic effect, especially at a late stage of the disease, when a dose reduction of levodopa is indicated.

Discontinuation of treatment. Pramipexole should be discontinued gradually over several days.

Doses for patients receiving concomitant levodopa therapy. With simultaneous therapy with levodopa, it is recommended that the dose of levodopa be reduced as the dose is increased, as well as during maintenance therapy with pramipexole. This is necessary to avoid excessive dopaminergic stimulation.

Doses for patients with renal failure. For initial therapy: in patients with Cl creatinine above 50 ml / min, a reduction in the daily dose or frequency of administration is not required. 

With Cl creatinine 20-50 mg / ml, the initial daily dose of the drug is prescribed in 2 doses, starting with 0.125 mg 2 times a day (0.25 mg / day). Do not exceed the maximum daily dose of 2.25 mg of pramipexole. With Cl Creatinine

If renal function decreases during maintenance therapy, the daily dose of the drug is reduced by the same percentage by which creatinine clearance decreases, i.e. if creatinine clearance is reduced by 30%, the daily dose should be reduced by 30%. 

The daily dose can be divided into two doses if Cl creatinine is in the range of 20-50 ml / min, and taken once a day if Cl creatinine is less than 20 ml / min.

Doses for patients with liver failure. There is no need to reduce the dose in patients with liver failure.

Symptomatic treatment of idiopathic restless legs syndrome:

Initial therapy. The recommended initial daily dose is 0.125 mg, 2-3 hours before bedtime. If patients require an additional reduction in symptoms, the dose can be increased every 4-7 days to a maximum dose of 0.75 mg per day

Maintenance therapy An individual dose should be in the range from 0.125 to 0.75 mg / day.

Discontinuation of treatment. Treatment can be stopped without a gradual dose reduction. In clinical studies, only 10% of patients showed signs of aggravation of symptoms after a sharp cessation of treatment, this effect was manifested at any dosage.

Doses for patients with renal failure. Withdrawal of the drug depends on renal function and is directly correlated with creatinine clearance. Based on pharmacokinetic studies in patients with renal failure, for patients with Cl creatinine greater than 20 ml / min, a daily dose reduction is not required. The use of Mirapex ^®  in patients with restless legs syndrome suffering from renal failure has not been studied.

Doses for patients with liver failure. The need to reduce the dose in patients with liver failure is not considered, since approximately 90% of the absorbed drug is excreted through the kidneys.

Dose for children and adolescents. The safety and effectiveness of Mirapex ^®  in children and adolescents under the age of 18 years have not been established.

Symptoms: not established. Clinical experience with a significant overdose of Mirapex is absent. One patient with a 10-year history of schizophrenia took 11 mg / day of pramipexole for 2 days; it is 2-3 times more than the recommended daily dose protocol. 

There were no adverse effects due to an increase in dose. Blood pressure remained stable, although heart rate increased to 100-120 beats / min.

Treatment: pramipexole antidote is unknown. When symptoms of central nervous system stimulation appear, neuroleptics, derivatives of phenothiazine or butyrophenone, can be used, however, the effectiveness of these drugs in eliminating the effects of an overdose of Mirapex has not been evaluated. 

In the treatment of overdose, maintenance therapy, gastric lavage, the use of rehydration and detoxification agents, and ECG monitoring may be required.

During treatment with pramipexole, episodes of sudden falling asleep against the background of daytime wakefulness were noted. Drowsiness usually develops when using Mirapex in doses of more than 1.5 mg / day. 

Episodes of sudden falling asleep against the background of daytime wakefulness arise against the background of already developed drowsiness. Factors that increase the risk of drowsiness include: concomitant use of sedatives, sleep disorders, concomitant use of drugs that increase plasma levels of pramipexole (e.g., cimetidine). 

Before prescribing Mirapex, the doctor must determine the presence of these risk factors. During therapy, it is necessary to monitor the patient's condition to identify a tendency to drowsiness. 

With the development of severe drowsiness in the daytime or the appearance of episodes of sudden falling asleep against the background of daytime wakefulness, which require active intervention, Mirapex should be discontinued. If it is necessary to continue therapy, the dose of the drug should be reduced and the patient should be advised to refrain from driving and other potentially dangerous activities.

During treatment with Mirapex, the incidence of arterial hypotension, as a rule, did not increase compared with placebo.

Elderly patients (65 years and older) require dose adjustment of Mirapex.

Since pramipexole is excreted by the kidneys, patients with kidney disease may require dose adjustment. 

Influence on the ability to drive vehicles and control mechanisms

The patient should refrain from driving and other potentially dangerous activities until the nature of the effect of the drug on the ability to concentrate and the speed of psychomotor reactions is established.

Pediatric Use

The safety and effectiveness of the use of Mirapex in children has not been established.