Mirapex PD prolonged-release tablets 0.375mg, No. 10

• symptomatic treatment of idiopathic Parkinson's disease (the drug can be used as monotherapy or in combination with levodopa).

Extended-release tablets should be taken 1 time / day, at approximately the same time of the 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 the time of the next intake of the drug was missed, then if more than 12 hours have not passed since the usual time of administration, the drug should be taken in a daily dose. If more than 12 hours have passed, then the drug should not be taken, the next appointment should take place the next day at the usual time.

Patients who are already taking Mirapex tablets can be transferred to taking MirapexЃ PD prolonged-release tablets during the day, at the same dose.

Initial therapy:

As presented below, the dose should be gradually increased, starting with a starting dose of 0.375 mg / 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 a further dose increase is necessary, the daily dose is increased by 0.75 mg at weekly intervals to a maximum dose of 4.5 mg / day.

Supportive treatment:

The therapeutic dose should be in the range from 0.375 mg to a maximum dose of 4.5 mg / day. In the main studies carried out in the initial and advanced stages of the disease, during the dose increase, the effectiveness of treatment was observed starting from a daily dose of 1.5 mg. This does not exclude the possibility that in some patients, a daily dose above 1.5 mg may lead to an additional therapeutic effect.

This applies in part to patients with advanced disease who have been shown to reduce the dose of levodopa.

Termination of treatment:

The dose of the drug should be reduced by 0.75 mg / day, until the daily dose reaches 0.75 mg. After that, the dose should be reduced by 0.375 mg / day.

Combined treatment with levodopa

With 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 to prevent excessive dopaminergic stimulation.

Application for renal failure

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

With initial therapy in patients with CC above 50 ml / min, a decrease in the daily dose or frequency of administration is not required.

In patients with CC from 30 to 50 ml / min, treatment should be started 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 evaluated. If further dose increases are required, the daily dose should be increased by 0.375 mg of pramipexole at weekly intervals to a maximum dose of 2.25 mg of pramipexole / day.

There are no data on the treatment with sustained-release tablets in patients with CC below 30 ml / min. The feasibility of using conventional-release tablets should be investigated.

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

Application for liver failure

There is no need to reduce the dose in patients with hepatic impairment.

Use in children and adolescents

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

Active substance:

pramipexole dihydrochloride monohydrate - 0.375 mg, which corresponds to the content of pramipexole - 0.26 mg

Excipients: hypromellose 2208 - 112.5 mg, corn starch - 119.375 mg, carbomer 941 - 15 mg, colloidal silicon dioxide - 1.5 mg, magnesium stearate - 1.25 mg.

• children and adolescents up to 18 years old;

• hypersensitivity to pramipexole or to any component of the drug.

The drug should be used with caution in renal failure, lowering blood pressure.

Trade name:

Mirapex PD

International non-proprietary name:

pramipexole

Dosage form:

extended-release tablets

Clinical and pharmacological group: Antiparkinsonian drug - a stimulant of dopaminergic transmission in the central nervous system

Pharmaco-therapeutic group: Dopamine receptor agonist

pharmachologic effect

An antiparkinsonian drug - a dopamine receptor agonist. With high selectivity and specificity, it 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.

Pramipexole in vitro protects neurons from the neurotoxicity of levodopa.

Reduces the secretion of prolactin (dose-dependent).

In clinical studies on healthy volunteers in whom the dose of MirapexЃ 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. In studies on patients, this effect was not observed.

Pharmacokinetics

Absorption 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 eating a fatty meal, there is a slight increase, by about 20%, in Cmax and a slowdown, by about 2 hours, in the time to reach Cmax, which have 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 tissues (approximately 8 times higher than in plasma).

Metabolism and excretion

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. T1 / 2 ranges from 8 hours in young people and up to 12 hours in older people.

Indications

• symptomatic treatment of idiopathic Parkinson's disease (the drug can be used as monotherapy or in combination with levodopa).

Dosage regimen

Extended-release tablets should be taken 1 time / day, at approximately the same time of the 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 the time of the next intake of the drug was missed, then if more than 12 hours have not passed since the usual time of administration, the drug should be taken in a daily dose. If more than 12 hours have passed, then the drug should not be taken, the next appointment should take place the next day at the usual time.

Patients who are already taking Mirapex tablets can be transferred to taking MirapexЃ PD prolonged-release tablets during the day, at the same dose.

Initial therapy:

As presented below, the dose should be gradually increased, starting with a starting dose of 0.375 mg / 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 a further dose increase is necessary, the daily dose is increased by 0.75 mg at weekly intervals to a maximum dose of 4.5 mg / day.

Supportive treatment:

The therapeutic dose should be in the range from 0.375 mg to a maximum dose of 4.5 mg / day. In the main studies carried out in the initial and advanced stages of the disease, during the dose increase, the effectiveness of treatment was observed starting from a daily dose of 1.5 mg. This does not exclude the possibility that in some patients, a daily dose above 1.5 mg may lead to an additional therapeutic effect.

This applies in part to patients with advanced disease who have been shown to reduce the dose of levodopa.

Termination of treatment:

The dose of the drug should be reduced by 0.75 mg / day, until the daily dose reaches 0.75 mg. After that, the dose should be reduced by 0.375 mg / day.

Combined treatment with levodopa

With 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 to prevent excessive dopaminergic stimulation.

Application for renal failure

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

With initial therapy in patients with CC above 50 ml / min, a decrease in the daily dose or frequency of administration is not required.

In patients with CC from 30 to 50 ml / min, treatment should be started 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 evaluated. If further dose increases are required, the daily dose should be increased by 0.375 mg of pramipexole at weekly intervals to a maximum dose of 2.25 mg of pramipexole / day.

There are no data on the treatment with sustained-release tablets in patients with CC below 30 ml / min. The feasibility of using conventional-release tablets should be investigated.

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

Application for liver failure

There is no need to reduce the dose in patients with hepatic impairment.

Use in children and adolescents

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

Side effect

When using the drug, the following side effects are listed: 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 cravings for 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 , peripheral edema; pneumonia; itching, rash and other hypersensitivity reactions; anxiety, 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 blood pressure lowering during treatment with MirapexЃ PD is no more than with placebo treatment. However, hypotension can be observed in some patients at the beginning of treatment, especially if the doses of the drug are increased too quickly. Libido disorders (increase or decrease) may be associated with treatment with MirapexЃ PD.

Patients taking pramipexole tablets have reported falling asleep suddenly during daytime activities, including driving, sometimes resulting in traffic accidents. At the same time, some of them did not report the presence of alarming signs, such as drowsiness, often observed in patients taking pramipexole tablets at doses higher than 1.5 mg / day, which, according to current knowledge about the physiology of sleep, always lead to sudden falling asleep. There was no clear relationship with the duration of treatment. At the same time, some of the patients also took other drugs with potentially sedative properties. In most cases where such information was available, there were no such episodes after dose reduction or discontinuation of treatment. Patients with Parkinson's disease treated with dopamine agonists, including MirapexЃ PD,especially in high doses, pathological cravings for gambling, increased libido and hypersexuality have been reported, which usually resolved after dose reduction or discontinuation of treatment.

In clinical trials and post-marketing surveillance, heart failure has been reported in patients taking pramipexole. A causal relationship between pramipexole treatment and heart failure has not been proven.

Contraindications for use

• children and adolescents up to 18 years old;

• hypersensitivity to pramipexole or to any component of the drug.

The drug should be used with caution in renal failure, lowering blood pressure.

Application during pregnancy and lactation

The possibility of using the drug during 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. 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 inhibits lactation. Therefore, the drug should not be taken during breastfeeding.

The effect on fertility in humans has not been studied. Animal studies do not indicate direct or indirect evidence of adverse effects on fertility in males.

Application for violations of liver function

There is no need to reduce the dose in patients with hepatic impairment.

Application for impaired renal function

With caution in renal failure.

Application in children

Contraindicated in children under 18 years of age.

special instructions

When prescribing the drug MirapexЃ PD to patients with renal insufficiency, a dose reduction is recommended.

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

Hallucinations are more often observed during treatment with MirapexЃ PD in combination with levodopa in patients with advanced Parkinson's disease than with 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 affect their ability to drive.

Patients and their caregivers should be aware that in connection with the treatment of patients with dopaminergic drugs, there may be signs of abnormal behavior (symptoms of impulsive and compulsive actions), such as a tendency to overeat, an obsessive desire to shop (pathological shopping), hypersexuality and pathological gambling. In such cases, a dose reduction / discontinuation decision should be considered.

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 severe cardiovascular disease. Due to the risk of orthostatic hypotension during dopaminergic therapy, it is recommended to control blood pressure, especially at the beginning of treatment.

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

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 unknown.

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.

There are reports that with a sudden cessation of therapy with dopaminergic drugs, symptoms of neuroleptic malignant syndrome may be observed.

Influence on the ability to drive vehicles and use mechanisms

ѕациенты должны быть информированы о возможности возникновени¤ галлюцинаций (в основном зрительных), которые могут вли¤ть на способность к вождению автомобил¤.

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 серьезными 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 ѕ?, чтобы оценить вли¤ет ли он отрицательно или нет на их умственную и/или двигательную активность. ѕациентам должно быть рекомендовано что, если во врем¤ лечени¤ они испытывают повышенную сонливость или эпизоды засыпани¤ во врем¤ повседневной де¤тельности (т.е. во врем¤ разговора, еды и т.д.), то они должны отказатьс¤ от управлени¤ автомобилем, работы с техникой, и обратитьс¤ к врачу.

ѕередозировка

—лучаи выраженной передозировки не описаны.

ѕредполагаемые симптомы, свойственные фармакодинамическому профилю агонистов допаминовых рецепторов: тошнота, рвота, гиперкинези¤, галлюцинации, возбуждение и снижение ј?.

Ћечение: установленного антидота не существует, при передозировке рекомендуетс¤ промывание желудка, симптоматическа¤ терапи¤, динамическое наблюдение. Ёффективность проведени¤ гемодиализа не установлена. ѕри признаках возбуждени¤ ?Ќ— возможно назначение нейролептиков.

Ћекарственное взаимодействие

ѕрамипексол в незначительной степени (<20%) св¤зываетс¤ с белками плазмы и подвергаетс¤ биотрансформации. ѕоэтому взаимодействи¤ с другими лекарствами, вли¤ющими на св¤зывание с белками плазмы, или выведение за счет биотрансформации маловеро¤тны.

ѕрепараты, которые ингибируют активную секрецию катионных препаратов через почечные канальцы (например, циметидин), или которые сами вывод¤тс¤ за счет активной секреции через почечные канальцы, могут взаимодействовать с прамипексолом, что выражаетс¤ в снижении клиренса одного или обоих лекарств. ¬ случае одновременного применени¤ таких препаратов (в т.ч. амантадина) и прамипексола необходимо обращать внимание на такие признаки избыточной допаминовой стимул¤ции, как дискинези¤, возбуждение или галлюцинации. ¬ подобных случа¤х необходимо снизить дозу.

—елегилин и леводопа не вли¤ют на фармакокинетику прамипексола. ѕрамипексол не вли¤ет на общую величину абсорбции или элиминации леводопы. ¬заимодействие с антихолинергическими лекарственными средствами и амантадином не изучалось. ќднако взаимодействие с амантадином возможно, т.к. препараты имеют сходный механизм выведени¤. јнтихолинергические лекарственные средства, в основном, вывод¤тс¤ метаболическим путем, поэтому взаимодействие с прамипексолом маловеро¤тно.

ѕри увеличении дозы препарата у пациентов с болезнью ѕаркинсона рекомендуетс¤ снижение дозы леводопы, при этом дозу других противопаркинсонических лекарственных средств необходимо поддерживать на посто¤нном уровне.

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

Storage conditions of the drug

The drug should be stored in a dry place out of the reach of children at a temperature not exceeding 25 ? C.

Shelf life

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

Terms of sale

The drug is available with a prescription.

Contacts for inquiries

BERINGER INGELHEIM INTERNATIONAL GMBH (Germany)