Mirapex PD tablets prolong 1.5 mg No. 30

Compound

One Mirapex tablet contains 0.25 mg or 1 mg pramipexole monohydrate dihydrochloride (0.18 mg or 0.7 mg pramipexole ).
Additionally: colloidal silicon dioxide, magnesium stearate, mannitol, povidone, corn starch. One tablet of Mirapex PD (extended release) includes 0.375 mg / 0.75 mg / 1.5 mg / 3 mg / 4.5 mg pramipexole dihydrochloride monohydrate (0.26 mg / 0.52 mg / 1.05 mg / 2. 1 mg / 3.15 mg pramipexole ). Additionally: corn starch, hypromellose 2208, colloidal silicon dioxide, carbomer 941, magnesium stearate.

Description of the dosage form

Tablets 0.25 mg: oval, white, with a beveled edge, flat on both sides. On one side of the tablet there is a deep score, on both sides of which there is a marking “P7”, on the other side of the tablet there is a score, on both sides of which there is a marking of the company logo.

1 mg tablets: round, white, with a beveled edge, flat on both sides. On one side of the tablet there is a deep score, on both sides of which there is a marking “P9”, on the other side of the tablet there is a score, on both sides of which there is a marking of the company logo.

Pharmacodynamics and pharmacokinetics

The dopamine receptor agonist pramipexole has a high specific and selective ability to bind to the D2 subgroup of dopamine receptors , of which the most pronounced affinity is for D3 receptors. By stimulating dopamine receptors located in the striatum, the drug helps reduce the patient's lack of motor activity observed in Parkinson's disease .

Characteristic of pramipexole is its inhibitory effect on the synthesis, subsequent release and further metabolism of dopamine . In vitro, pramipexole protects dopamine neurons from the process of their degeneration that develops with methamphetamine neurotoxicity or ischemia .

Treatment of restless legs syndrome with Mirapex (RLS) has not been fully studied, since the pathophysiology of this painful condition is not fully known. Despite this, there is neuropharmacological evidence of the primary involvement of the dopaminergic system . Studies using PET (positron emission tomography) have revealed the possibility of moderate dopaminergic presynaptic dysfunction the pathogenesis of RLS.

In vitro , pramipexole protects neurons from the neurotoxic effects of levodopa . Depending on the dose taken, it reduces the secretion of prolactin .

Long-term use of the drug (more than 3 years) for the treatment of patients suffering from Parkinson's disease , as well as its treatment of patients with RLS for 1 year, did not reveal signs of a decrease in its effectiveness.

When taken orally, pramipexole is absorbed from the gastrointestinal tract quite quickly. Plasma Cmax is observed after approximately 120 minutes. The absolute bioavailability rate exceeds 90%. The extent of absorption of pramipexole is independent of its administration with food, but increases the time to reach plasma Cmax by approximately 60 minutes. Css is observed 48 hours after starting Mirapex.

Pramipexole has a wide distribution in the human body, Vd is approximately 500 liters (with a variation of 20%). Approximately 15% of the drug is bound to plasma proteins. There is an accumulation of pramipexole in erythrocytes , as evidenced by the ratio of its concentrations in erythrocytes compared to plasma concentrations of 2. In healthy young volunteers, T1/2 of the drug is 8 hours, in elderly volunteers – 12 hours.

Pramipexole is excreted primarily by the kidneys; 90% of the drug is determined in the urine almost entirely in unchanged form. Extrarenal routes of excretion of pramipexole may play some role in its elimination, although no products of its metabolism have been identified in urine or plasma. Renal clearance of the drug is approximately 400 ml/min (with a variation of 25%), which is approximately three times the glomerular filtration . Thus, secretion of pramipexole occurs via the renal tubules , possibly via the organic cation transport system.

In women, the clearance rate of pramipexole is approximately 30% lower than in men, although this difference may largely depend on differences in weight. There is no difference in T1/2 values ​​between women and men.

The clearance rate of pramipexole decreases with age. In elderly patients (after 65 years), T1/2 of the drug increases by approximately 40% (from 8.5 hours to 12 hours). Compared to healthy young volunteers (<40 years of age), the total clearance of pramipexole is reduced by approximately 30%.

In patients with Parkinson's disease , compared with healthy elderly volunteers, a decrease in pramipexole clearance of up to 30% was observed. The reason for this difference in rates may be the reduced renal function noted in Parkinson's disease .

The pharmacokinetic properties of pramipexole in patients with hepatic impairment have not been studied. Due to 90% excretion of the drug by the kidneys in unchanged form, it can be assumed that there is no significant effect of impaired hepatic function on the excretion of pramipexole.

In case of severe impairment of renal function (with CC 20 ml/min), there is a decrease in the clearance of pramipexole by approximately 75%; in case of impairment of renal function (with CC 40 ml/min), clearance decreases by 60%. Patients in these categories need to reduce the initial and maintenance dosages of Mirapex. In patients undergoing hemodialysis , an extremely low clearance of pramipexole , since a small amount is excreted during dialysis.

The pharmacokinetics of pramipexole have not been studied in the pediatric age group.

Pharmacological properties of the drug Mirapex

Pharmacodynamics. Pramipexole, the active component of Mirapex, is a dopamine agonist with high selectivity and specificity for dopamine receptors of the D2 subtype and has a predominant affinity for D3 receptors. Mirapex alleviates parkinsonian movement disorders by stimulating dopamine receptors in the striatum. Animal studies have demonstrated that pramipexole inhibits the synthesis, release and metabolism of dopamine. Pramipexole protects dopamine neurons from degeneration in response to ischemia or methamphenamine neurotoxicity. In vitro studies have shown that pramipexole protects neurons from the neurotoxic effects of levodopa. The exact mechanism of action of Mirapex in the treatment of restless legs syndrome is not known. Although the pathophysiology of restless legs syndrome is not generally established, neuropharmacological evidence points to the involvement of the primary dopaminergic system. Studies using positron emission tomography indicate the possible influence of minor dysfunction of the striatal presynaptic dopaminergic system on the pathogenesis of restless legs syndrome. In studies conducted on volunteers, a dose-dependent decrease in serum prolactin levels was noted. Parkinson's disease In controlled clinical studies, the effectiveness of Mirapex was maintained throughout the study, about 6 months. In open studies that lasted more than 3 years, there were no signs of a decrease in the effectiveness of the drug. Restless legs syndrome Mirapex was evaluated in four placebo-controlled studies involving approximately 1,000 patients with moderate to severe restless legs syndrome. Efficacy was demonstrated during controlled studies in patients whose treatment lasted up to 12 weeks, and long-term effectiveness was noted over a 9-month period. The effectiveness of Mirapex was maintained during open-label extension studies of approximately 1 year. Pharmacokinetics. Pramipexole is rapidly and completely absorbed after oral administration. Absolute bioavailability is more than 90%, the maximum concentration in the blood plasma is recorded between 1–3 hours. The rate of absorption decreases with food intake, but this does not affect the overall level of absorption. Pramipexole exhibits linear kinetics and relatively minor fluctuations in plasma levels between patients. In humans, the binding of pramipexole to blood proteins is very low (≤20%), and the volume of distribution is large (400 L). In studies in rats, high concentrations of the drug were noted in brain tissue (approximately 8 times higher than in plasma). Pramipexole is metabolized in humans only in small amounts. Excretion through the kidneys of unchanged pramipexole is the most important route of elimination and accounts for about 80%. About 90% of the 14C-labeled dose is excreted in the urine, while less than 2% is detected in the feces. The total clearance of pramipexole is about 500 ml/min, and the renal clearance is about 400 ml/min. The half-life is from 8 hours in young people to 12 hours in elderly people.

Contraindications

Mirapex is contraindicated in patients with personal hypersensitivity to pramipexole or other components of the tablets, as well as in patients under the age of 18 years.

low blood pressure and renal failure , as well as lactating and pregnant women require careful use of the drug

Side effects

Therapy using Mirapex can lead to the following negative side effects:

• decreased appetite;
• abnormal dreams;
• fainting;
• amnesia;
• itching / rash and other hypersensitivity ;
• behavioral disorders (symptoms of compulsive and impulsive actions, including hypersexuality , overeating , obsessive shopping , pathological addiction to gambling , etc.);
• heart failure;
• weight loss/gain;
• confusion;
• decreased visual acuity/clarity;
• constipation;
• anxiety;
• rave;
• drowsiness;
• hyperkinesia;
• dizziness;
• hiccups;
• dyskinesia;
• headache;
• hyperphagia;
• dyspnea;
• sudden falling asleep;
• fatigue;
• pneumonia;
• hallucinations;
• visual impairment (including diplopia);
• decrease in blood pressure;
• paranoia;
• decreased secretion of antidiuretic hormone;
• peripheral edema;
• insomnia;
• nausea, vomiting;
• sexual desire disorder.

Side effects of the drug Mirapex

The following side effects have been recorded during the use of Mirapex: behavioral and sleep disturbances, confusion, constipation, mania, dizziness, dyskinesia, fatigue, hallucinations, headache, hyperkinesia, hypotension, increased appetite (overeating, hyperphagia), insomnia, impaired libido (increased or decrease), nausea, peripheral edema, paranoia, pathological gambling, drowsiness, weight gain, and sudden attacks of drowsiness. Hypotension may occur in some patients at the beginning of treatment, especially if Mirapex is titrated very quickly. Among patients treated with pramipexole, cases of falling asleep during daytime activities, including driving, have been reported, which in some cases has resulted in motor vehicle accidents. Drowsiness is common in patients taking pramipexole tablets in doses greater than 1.5 mg of pramipexole dihydrochloride monohydrate per day and always precedes sudden sleep onset. A clear connection between this phenomenon and the duration of treatment has not been established; some patients were taking other drugs with potential sedative properties. In most cases, further episodes of sudden sleep onset decreased or disappeared after dose reduction or discontinuation of drug treatment. Taking Mirapex, like other dopamine agonists, especially in high doses, can lead to pathological gambling, which disappears after discontinuation of the drug.

Mirapex tablets, instructions for use (Method and dosage)

Mirapex tablets are intended for oral (inside) administration with water and regardless of meal time. All daily dosages of the drug in milligrams are calculated using pramipexole dihydrochloride monohydrate and evenly divided into 3 doses.

Instructions for use of Mirapex in the treatment of Parkinson's disease

The first week of therapy using Mirapex is indicated at a daily dose of 0.375 mg divided into three doses of 0.125 mg. If the treatment is insufficiently effective, in the second week you can increase the daily dosage to 0.75 mg (0.25 mg three times), and in the third week to 1.5 mg (0.5 mg three times). In the future, it is possible to increase the daily dosage of the drug by 0.75 mg per week, up to reaching the maximum daily dose of 4.5 mg. Such a gradual increase (once every 5-7 days) of daily doses is carried out in order to reduce possible side effects of Mirapex and is carried out until the optimal therapeutic effect of therapy is obtained.

Maintenance treatment is carried out using individually selected daily dosages of Mirapex, ranging from 0.375 mg to 4.5 mg. At all stages of the disease (from early to late), the effectiveness of the drug was observed, starting with a daily dosage of 1.5 mg. At the same time, in some patients, the possibility of an additional therapeutic effect of Mirapex therapy at a daily dose exceeding 1.5 mg cannot be excluded, especially at a late stage of disease development, when a reduction in levodopa .

Termination of therapy with Mirapex is carried out by a gradual daily reduction of its daily dosage by 0.75 mg until a daily dose of 0.75 mg is reached, after which the dose is reduced by another 0.375 mg.

With parallel therapy with levodopa, it is recommended that as the dosage of Mirapex increases, as well as during maintenance treatment, the dose of levodopa in order to prevent excessive dopaminergic stimulation of the body.

For kidney pathologies , initial therapy with Mirapex for patients with creatinine clearance greater than 50 ml/min is carried out in the dosage regimen recommended above. With CC 20-50 ml/min, the daily initial dosage of the drug should be reduced by a third and amount to 0.25 mg (0.125 mg twice every 24 hours). The maximum permissible daily maintenance dose of Mirapex for such patients should not exceed 2.25 mg. When CC is less than 20 ml/min, a single dose of the drug per day is prescribed, starting with a dose of 0.125 mg. Such patients can take a maximum of 1.5 mg of Mirapex per 24 hours as a maintenance dose.

In case of a decrease in renal function during maintenance treatment, the daily dose of Mirapex should be reduced by the percentage of reduction in creatinine clearance (that is, if the creatinine clearance decreases by 30%, reduce the dose of the drug by 30%). With a CC of 20-50 ml/min, the daily dosage of Mirapex is divided into two doses; with a CC of less than 20 ml/min, the daily dose is taken once.

need to adjust the dosage regimen for the treatment of patients with liver pathologies .

Instructions for use of Mirapex in the treatment of restless legs syndrome

When treating this pathology, Mirapex is initially prescribed in a daily dosage of 0.125 mg, with a single dose taken 2-3 hours before bedtime. If it is necessary to further reduce the negative symptoms of the disease, the daily dose can be gradually increased every 4-7 days, initially to 0.25 mg, then to 0.5 mg and to a maximum of 0.75 mg.

Maintenance treatment is carried out in an individually selected daily dose of Mirapex, ranging from 0.125 mg to 0.75 mg.

Discontinuation of therapy does not require a gradual reduction in drug dosage. In clinical studies, the phenomenon of worsening negative symptoms of the disease after immediate cessation of therapy at any daily dose was observed in only 10% of patients.

In case of kidney pathologies, the excretion of pramipexole depends on their functional state and is determined by CK indicators. The results of pharmacokinetic studies in patients with insufficiency of renal function (with CC greater than 20 ml/min) showed no need to adjust the dosage regimen. Mirapex has not been studied in patients with RLS and poor renal function .

In case of liver pathologies , a reduction in Mirapex doses is not required, due to the fact that about 90% of the absorbed active ingredient of the drug is excreted in the urine.

The safety and effectiveness of Mirapex for the treatment of patients in the pediatric age group (up to 18 years) has not been established.

Pharmacokinetics

Pramipexole is rapidly and completely absorbed after oral administration. Absolute bioavailability is more than 90%, and Cmax in plasma is observed after 1-3 hours. The rate of absorption decreases with food intake, but the total amount of absorption is not affected by food intake. Pramipexole exhibits linear kinetics and relatively little interpatient variability in concentrations.

Pramipexole binds to proteins to a very small extent (<20%) and has a large Vd (400 L). Metabolized to a small 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, the renal clearance is about 400 ml/min. T1/2 ranges from 8 hours in young people to 12 hours in older people.

Overdose

Episodes of severe overdose during treatment with Mirapex have not been described. Presumably, when taking excessive dosages of the drug, negative symptoms characteristic of the pharmacodynamic profile of dopamine receptor agonists may appear: agitation , nausea/vomiting, hallucinations , hyperkinesia , decreased blood pressure.

There is no antidote to pramipexole. Treatment of cases of overdose should include cleansing of the gastrointestinal tract , dynamic observation and symptomatic therapy. The effectiveness of hemodialysis has been questioned. In case of observation of central nervous system excitation antipsychotics is allowed .

Mirapex drug overdose, symptoms and treatment

symptoms: there is no clinical experience of significant overdose. Expected side effects are related to the pharmacodynamic profile of the dopamine agonist and include nausea, vomiting, hyperkinesia, hallucinations, agitation and hypotension. Treatment: There is no established antidote for dopamine agonist overdose. If signs of central nervous system excitation appear, antipsychotics are prescribed. It is necessary to carry out general supportive measures, gastric lavage, and ECG monitoring. The effectiveness of hemodialysis has not been proven.

Interaction

Since the binding of pramipexole to plasma proteins is insignificant (less than 20%), and also due to the low biotransformation of this drug, its interaction with other therapeutic agents that affect protein bonds or elimination due to the biotransformation process is unlikely.

Drugs that inhibit the secretion of cationic substances through the renal tubules ( Cimetidine ), as well as drugs that are independently excreted by the renal tubules, can interact with the active ingredient of Mirapex - pramipexole and lead to a decrease in the clearance of one drug or both drugs. When using such drugs (including amantadine ) in parallel with pramipexole, you need to pay attention to the phenomena of excessive dopamine stimulation (overexcitation, hallucinations , dyskinesia ) and adjust the dosage regimen of therapy in a timely manner.

Selegiline and levodopa do not affect the pharmacokinetic parameters of pramipexole, which, in turn, does not affect the overall parameters of absorption and excretion of levodopa.

The interaction of pramipexole with anticholinergic medications and amantadine has not been specifically studied. However, due to a similar elimination mechanism, interaction between pramipexole and amantadine is possible. Anticholinergic drugs are mainly subject to metabolic transformations, and therefore their interaction with pramipexole is questionable.

When increasing the dosage of pramipexole, it is recommended to reduce the dose of co-administered levodopa. Dosages of other antiparkinsonian drugs are maintained at a constant level.

Due to the possibility of cumulative effects, caution should be exercised when taking ethanol or sedatives , as well as drugs that increase the plasma concentration of pramipexole ( cimetidine ).

During treatment with pramipexole, concomitant use of antipsychotic drugs (for example, if antagonism ).

special instructions

Manifestations of hallucinations and confusion are the most well-known side effects when taking dopamine agonists (including Mirapex) and levodopa . In the case of parallel administration of pramipexole and levodopa at a late stage of the disease, manifestations of hallucinations were observed more often, compared with Mirapex monotherapy in patients at an early stage of the disease. Patients taking Mirapex should be informed about the possibility of developing hallucinations (usually visual), which may affect their ability to perform hazardous work and drive a car.

Patients undergoing therapy with dopaminergic drugs , as well as their caregivers, should be aware of the possibility of symptoms of abnormal behavior (symptoms of compulsive and impulsive actions), including: hypersexuality , hyperphagia (overeating), pathological shopping (constant desire to buy), and pathological passion for gambling . If these abnormal symptoms occur, a decision should be made to reduce the dose of Mirapex and possibly gradually discontinue therapy.

In patients with psychotic disorders, the use of pramipexole in combination with dopamine agonists is possible only with an adequate assessment of the risk/benefit ratio of such treatment. The combined use of antipsychotic medications and pramipexole should be avoided.

At the stage of treatment with Mirapex, it is recommended to check the patient’s vision at regular intervals. Also, if there are visual disturbances, a vision test should be performed immediately after the first dose of the drug.

cardiovascular pathologies require careful use of Mirapex . Due to the possible formation of orthostatic hypotension , during treatment with dopaminergic drugs, the patient’s blood pressure should be monitored, especially at the beginning of therapy.

Patients should be warned about the possibility of the sedative effect of Mirapex. There are reports of a feeling of drowsiness and subsequent sudden falling asleep during the patient's normal daily activities (including hazardous work and driving), noted at any stage of therapy.

Epidemiological studies have revealed an increased risk of melanoma in patients with Parkinson's disease (2-6 times higher compared to the general population). It is not known whether this increase in the risk of melanoma Parkinson's disease itself , or is associated with other factors, including the use of medications used to treat this pathology. For the above reasons, patients and their caregivers should be informed about the possible formation of melanoma while taking dopaminergic drugs, including pramipexole.

It has been reported that in the treatment of Parkinson's disease, abrupt cessation of dopaminergic drugs led to the development of negative symptoms similar to those of neuroleptic malignant syndrome .

Reports in the literature suggest that restless legs syndrome when treated with dopaminergic drugs. This increase was manifested by an earlier onset of the development of evening symptoms of the disease (sometimes already after lunch) and the spread of similar negative phenomena to other limbs. However, 26-week clinical controlled trials examining this particular effect did not reveal a significant difference in the increase in clinical symptoms of RLS between the pramipexole and placebo .

Patients should be informed about the potential for the formation of hallucinations (usually visual), which negatively affect the ability to drive vehicles. When taking Mirapex, a sedative effect of the drug may be observed, manifested by a feeling of drowsiness and instant falling asleep during everyday life. Due to the fact that drowsiness is a fairly common negative effect of therapy with dopaminergic drugs and can lead to potentially fatal consequences, patients should refrain from hazardous work and driving until they have gained sufficient experience with Mirapex therapy and are able to adequately assess its effect on their own motor and/or or mental activity . drowsiness during everyday life or sudden falling asleep (while eating, talking, etc.) during treatment, patients are not recommended to engage in hazardous work or driving vehicles.

Mirapex PD tablets prolong 1.5 mg No. 30

Compound

Active substance: pramipexole dihydrochloride monohydrate - 1.5 mg. Excipients: hypromellose 2208 - 157.5 mg, corn starch - 169.65 mg, carbomer 941 - 17.5 mg, colloidal silicon dioxide - 2.1 mg, magnesium stearate - 1.75 mg.

Pharmacokinetics

Suction and distribution

Pramipexole is rapidly and completely absorbed after oral administration. Absolute bioavailability exceeds more than 90% and Cmax in plasma is reached after approximately 6 hours. As a rule, food intake does not affect the bioavailability of pramipexole. After ingestion of a fatty meal, there is a slight increase, approximately 20%, in Cmax and a slowdown, approximately 2 hours, in the time to reach Cmax, which has no clinical significance.

Pramipexole exhibits linear kinetics and relatively little variability in plasma levels between patients, regardless of pharmaceutical form. Pramipexole binds to plasma proteins to a very small extent (<20%) and has a large Vd (400 l). High concentrations of the drug were observed in rat brain tissue (approximately 8 times higher than in plasma).

Metabolism and excretion

Metabolized to a small 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, the renal clearance is about 400 ml/min. T1/2 ranges from 8 hours in young people to 12 hours in older people.

Indications for use

Symptomatic treatment of idiopathic Parkinson's disease in adults in the form of monotherapy (without levodopa) or in combination with levodopa, i.e. at all stages of the disease, including at a late stage, when the effect of taking levodopa decreases or becomes unstable, and fluctuations in the therapeutic effect occur (the “wear-out” phenomenon of the end of the dose and the “on-off” phenomenon).

Contraindications

• children and adolescents up to 18 years of age;
• hypersensitivity to pramipexole or to any component of the drug.

The drug should be used with caution in case of renal failure or decreased blood pressure.

Directions for use and doses

Mirapex PD should be taken once a day, at approximately the same time of day. The tablets are swallowed whole with water; the tablets must not be chewed, broken or crushed. The tablets can be taken with or without food.

If a dose of the drug is missed, it should be taken if no more than 12 hours have passed since the usual time of administration. If more than 12 hours have passed, the missed dose should not be taken; the next dose should be taken the next day at the usual time.

Patients who are already taking Mirapex tablets can be switched to Mirapex PD extended-release tablets within 24 hours, at the same dose.

Initial therapy:

As presented below, the dose should be gradually increased, starting with a starting dose of 0.375 mg per day, and then increased every 5-7 days. To prevent unwanted side effects, the dose should be adjusted until the maximum therapeutic effect is achieved.

If further dose increases are necessary, increase the daily dose by 0.75 mg at weekly intervals to a maximum dose of 4.5 mg per day.

Maintenance treatment:

Individual doses should range from 0.375 mg to a maximum dose of 4.5 mg per day. In the main studies conducted in the initial and advanced stages of the disease, during dose escalation, treatment effectiveness was observed starting with a daily dose of 1.5 mg. This does not exclude the possibility that in some patients, doses higher than 1.5 mg per day may lead to additional therapeutic benefits, especially in the later stages of the disease when a reduction in the dose of levodopa is indicated.

Stopping treatment:

With abrupt cessation of therapy with dopaminergic drugs, the development of neuroleptic malignant syndrome is possible, so the dose of the drug should be reduced by 0.75 mg per day until the daily dose reaches 0.75 mg. After this, the dose should be reduced by 0.375 mg per day (see section "Special Instructions").

Dose for patients receiving concomitant treatment with levodopa:

During simultaneous therapy with levodopa, it is recommended to reduce the dose of levodopa as the dose increases, as well as during maintenance therapy with pramipexole. This is necessary to prevent excessive dopaminergic stimulation.

Dose for patients with renal failure:

The elimination of pramipexole from the body depends on renal function.

In patients with creatinine clearance above 50 ml/min, a reduction in the daily dose or frequency of administration is not required.

In patients with creatinine clearance from 30 to 50 ml/min, treatment should begin with a dose of 0.375 mg of the drug every other day. After one week of therapy, before increasing the daily dose, precautions should be taken and the therapeutic response and tolerance should be carefully assessed. If further dose increases are necessary, the daily dose should be increased by 0.375 mg pramipexole at weekly intervals to a maximum dose of 2.25 mg pramipexole per day.

It is not recommended to treat patients with creatinine clearance below 30 mg/min since there are no data on treatment with extended-release tablets. The advisability of using the drug Mirapex tablets should be considered.

If renal function has decreased during maintenance treatment, follow the recommendations presented above.

Dose for patients with liver failure:

No dose reduction is required in patients with liver failure.

Dose for children and adolescents:

The safety and effectiveness of the drug in children and adolescents under 18 years of age has not been established.

Storage conditions

Store in original packaging at a temperature not exceeding 25°C, out of the reach of children.

Best before date

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

special instructions

When prescribing Mirapex® PD to patients with renal failure, a dose reduction is recommended.

Hallucinations and confusion are known side effects of dopamine agonist and levodopa treatment.

Hallucinations are more often observed during treatment with Mirapex® PD in combination with levodopa in patients with advanced Parkinson's disease than during monotherapy in patients with Parkinson's disease at an early stage of the disease. Patients should be informed that hallucinations (mainly visual) may develop. Patients should be warned that hallucinations may occur that may affect the ability to drive.

Patients and those caring for them should be aware that signs of abnormal behavior (symptoms of impulsive and compulsive actions), such as overeating, compulsive shopping (pathological shopping), may occur in connection with the treatment of patients with dopaminergic drugs. hypersexuality and pathological craving for gambling. In such cases, a decision to reduce the dose/gradually discontinue treatment should be considered.

In patients with psychotic disorders, the prescription of dopamine agonists in combination with pramipexole is possible only after a preliminary assessment of the possible risk-benefit. Concomitant use of pramipexole with antipsychotic drugs should be avoided.

It is recommended to check your vision at regular intervals or immediately after prescribing the drug if such disorders are present.

Caution must be exercised if the patient has severe cardiovascular disease. Due to the risk of orthostatic hypotension during dopaminergic therapy, it is recommended to monitor blood pressure, especially at the beginning of treatment.

Patients should be warned about the possible sedative effects of the drug, including drowsiness and sudden falling asleep during daytime activities. Patients should be advised that if they experience excessive sleepiness or episodes of sudden falling asleep during daytime activities (eg, talking, eating, etc.), which may occur at any time during treatment, they should not drive or participate in activities. potentially hazardous activities and should consult a physician.

Epidemiological studies have shown that patients with Parkinson's disease have a high risk (2 to approximately 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 unknown.

For the reasons given above, patients and those caring for them should be informed that while taking pramipexole or other dopaminergic drugs it is necessary to be alert to the possible development of melanoma.

There are reports that symptoms of neuroleptic malignant syndrome may occur if dopaminergic drug therapy is abruptly discontinued.

Description

An antiparkinsonian drug is a stimulator of dopaminergic transmission in the central nervous system.

Dosage form

Extended-release tablets are white or almost white, oval, biconvex, engraved with the company logo on one side and “P3” engraved on the other.

Use in children

Contraindicated in children under 18 years of age.

Pharmacodynamics

An antiparkinsonian drug is a dopamine receptor agonist. It binds with high selectivity and specificity to dopamine receptors of the D2 subgroup, of which it has the most pronounced affinity for D3 receptors. Reduces motor activity deficits 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 that occurs in response to ischemia or methamphetamine neurotoxicity.

Pramipexole protects neurons from levodopa neurotoxicity in vitro.

Reduces the secretion of prolactin (dose-dependent).

In clinical studies on healthy volunteers, in whom the dose of Mirapex® PD was increased faster than it should (every 3 days), up to 4.5 mg/day, an increase in blood pressure and heart rate was observed. This effect was not observed in patient studies.

Side effects

The following side effects are listed when using the drug: abnormal behavior (symptoms of impulsive and compulsive actions), such as a tendency to overeat (hyperphagia), compulsive shopping (pathological shopping), hypersexuality and pathological gambling; abnormal dreams, amnesia, heart failure, confusion, constipation, delirium, dizziness, dyskinesia, shortness of breath, weakness, hallucinations, headache, hiccups, hyperkinesia, hyperphagia, decreased blood pressure, impaired secretion of antidiuretic hormone, insomnia, libido disorders, nausea, paranoia , peripheral edema; pneumonia; itching, rash and other hypersensitivity reactions; restlessness, drowsiness, sudden falling asleep, fainting, blurred vision (including diplopia, decreased visual acuity and clarity of perception), vomiting, changes in body weight, including decreased appetite.

The incidence of decreased blood pressure during treatment with Mirapex® PD is no greater than during treatment with placebo. However, hypotension may occur in some patients early in treatment, especially if drug doses are increased too quickly. Libido disorders (increase or decrease) may be associated with treatment with Mirapex® PD.

Patients taking pramipexole tablets have reported sudden sleepiness during daytime activities, including driving, sometimes resulting in traffic accidents. At the same time, some of them did not report the presence of warning signs, such as drowsiness, often observed in patients taking pramipexole tablets in doses above 1.5 mg / day, which, according to modern knowledge of sleep physiology, always leads to sudden sleep onset. There was no clear relationship with treatment duration. At the same time, some patients were also taking other medications with potentially sedative properties. In most cases where such information was available, there were no similar episodes after dose reduction or discontinuation of treatment. Patients with Parkinson's disease treated with dopamine agonists, including Mirapex® PD, especially in high doses, reported pathological gambling, increased libido and hypersexuality, which usually resolved after dose reduction or cessation of treatment.

Heart failure has been reported in patients receiving pramipexole during clinical trials and post-marketing surveillance. A causal relationship between pramipexole treatment and heart failure has not been proven.

Within systemic organ classes, the following categories are used according to the frequency of side effects: very often (≥1/10); often (≥1/100, <1/10); uncommon (≥1/1000, <1/100); rare (≥1/10,000, <1/1000); very rare (<1/10,000); not installed.

Use during pregnancy and breastfeeding

Pregnancy

The effect on pregnancy and lactation in humans has not been studied.

The possible effects of pramipexole on reproductive function have been studied in animal experiments. Pramipexole does not show teratogenicity in rats and rabbits, but 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.

Breast-feeding

The excretion of the drug into breast milk in women has not been studied. The concentration of the drug in rat milk was higher than in plasma. Since pramipexole inhibits prolactin secretion, it can be assumed that it also suppresses lactation. Therefore, the drug should not be taken during breastfeeding.

Fertility

The effects on fertility in humans have not been studied. Results from animal studies do not indicate direct or indirect evidence of adverse effects on fertility in males.

Interaction

Pramipexole binds to plasma proteins to a small extent (<20%) and undergoes biotransformation. Therefore, interactions with other drugs that affect plasma protein binding or elimination through biotransformation are unlikely.

Drugs that inhibit active renal tubular secretion of cationic drugs (eg, cimetidine), or which are themselves eliminated by active renal tubular secretion, may interact with pramipexole resulting in decreased clearance of one or both drugs. In case of simultaneous use of such drugs (including amantadine) and pramipexole, it is necessary to pay attention to signs of excessive dopamine stimulation such as dyskinesia, agitation or hallucinations. In such cases, it is necessary to reduce the dose.

Selegiline and levodopa do not affect the pharmacokinetics of pramipexole. Pramipexole does not affect the overall absorption or elimination of levodopa. Interactions with anticholinergic drugs and amantadine have not been studied. However, interaction with amantadine is possible, because drugs have a similar mechanism of elimination. Anticholinergic drugs are primarily eliminated metabolically, so interactions with pramipexole are unlikely.

When increasing the dose of the drug in patients with Parkinson's disease, it is recommended to reduce the dose of levodopa, while the dose of other antiparkinsonian drugs must be maintained at a constant level.

Due to possible cumulative effects, patients should be advised to exercise caution when taking other sedative drugs or alcohol in combination with Mirapex® PD, as well as when taking drugs that increase the plasma concentration of pramipexole (for example, cimetidine).

Overdose

Cases of severe overdose have not been described.

The expected symptoms characteristic of the pharmacodynamic profile of dopamine receptor agonists are: nausea, vomiting, hyperkinesia, hallucinations, agitation and decreased blood pressure.

Treatment: there is no established antidote; in case of overdose, gastric lavage, symptomatic therapy, and dynamic observation are recommended. The effectiveness of hemodialysis has not been established. If there are signs of central nervous system excitation, antipsychotics may be prescribed.

Release form

Long-acting tablets 1.5 mg No. 30.

Impact on the ability to drive vehicles and operate machinery

Pramipexole may have a significant effect on the ability to drive or use machines. Hallucinations or drowsiness may occur.

Patients taking pramipexole who develop drowsiness and/or sudden sleep attacks should be advised to refrain from driving or engaging in activities in which, due to decreased alertness, they may expose themselves or others to the risk of serious injury or death ( for example, when working with machinery) until these symptoms disappear.

Mirapex's analogs

Level 4 ATC code matches:
Pramipexole

Pronoran

Bromocriptine

Analogues of Mirapex are represented by medicinal drugs similar to it in their main effect:

• Abergeen;
• Parlodel;
• Bromocriptine;
• Rolprina SR;
• Pronoran;
• Bromergon;
• Requip Modutab;
• Newpro;
• Oprymea.

During pregnancy and lactation

The effect of Mirapex on pregnant and lactating women has not been studied.

Studies carried out on animals to determine the effects of pramipexole on their reproductive function did not show a teratogenic effect of the drug, but revealed some embryotoxicity . In this regard, the use of Mirapex during pregnancy is allowed only in cases where the benefits of such treatment clearly exceed the possible risk to the fetus.

The excretion of pramipexole in the milk of nursing mothers has not been studied. Since one of the effects of pramipexole is the inhibition of prolactin , it is assumed to have a suppressive effect on lactation . For this reason, Mirapex should not be prescribed during breastfeeding .

Reviews about Mirapex

Reviews of Mirapex on forums dedicated to discussing medications used to treat Parkinson's disease , in comparison with reviews of other similar medications, are more positive. Relatives of patients observe a lower frequency and severity of side effects of Mirapex, including drowsiness and hallucinations , as well as greater effectiveness of this drug. Among the negative aspects of such treatment, one can note a gradual decrease in the effect of Mirapex, which leads to the need to search for its substitutes.

Mirapex price, where to buy

The average price of Mirapex is 260 rubles for 30 tablets of 0.25 mg and 900 rubles for 30 tablets of 1 mg.

On average, you can buy Mirapex PD for: 0.375 mg No. 30 – 140 rubles; 1.5 mg No. 30 – 1500 rubles; 3 mg No. 30 – 3000 rubles.

• Online pharmacies in RussiaRussia
• Online pharmacies in UkraineUkraine

ZdravCity

• Mirapex PD tablets prolonged action 0.375 mg 10 pcs. Boehringer Ingelheim
  RUB 129 order
• Mirapex PD prolonged action tablets 1.5 mg 30 pcs. Boehringer Ingelheim

  RUB 1,379 order

• Mirapex tablets 0.25 mg 30 pcs. Boehringer Ingelheim

  RUB 253 order

• Mirapex PD prolonged action tablets 3 mg 30 pcs. Boehringer Ingelheim

  RUB 2602 order

• Mirapex tablets 1 mg 30 pcs. Boehringer Ingelheim

  972 rub. order

Pharmacy Dialogue

• Mirapex (table 0.25 mg No. 30) Boehringer Ingelheim

  250 rub. order

• Mirapex PD (long-acting tablet 0.375 mg No. 10) Boehringer Ingelheim

  RUB 137 order

• Mirapex PD tablets long-acting 1.500 mg No. 30 Boehringer Ingelheim

  RUB 1,454 order

• Mirapex (table 1 mg No. 30) Boehringer Ingelheim

  RUR 997 order

• Mirapex PD extended-release tablets 3 mg No. 30Boehringer Ingelheim

  RUB 2,774 order

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Pharmacy24

• Mirapex PD 0.375 mg No. 30 tablets Boehringer Ingelheim Pharma GmbH & Co.
  KG, Nimechchina 534 UAH. order
• Mirapex PD 1.5 mg N30 tablets Boehringer Ingelheim Pharma GmbH & Co. KG, Nimechchina

  1811 UAH order

• Mirapex 1 mg No. 30 tablets Boehringer Ingelheim, Germany

  1585 UAH. order

• Mirapex PD 0.75 mg N30 tablets Boehringer Ingelheim Pharma GmbH & Co. KG, Nimechchina

  999 UAH order

• Mirapex 0.25 mg No. 30 tablets Boehringer Ingelheim, Germany

  442 UAH order