Mirapecs PD - instructions for use, doses, side effects, contraindications

Active substance: pramipexole dihydrochloride monohydrate 0.375 mg, 0.75 mg, 1.5 mg, 3.0 mg or 4.5 mg (equivalent to 0.26, 0.52, 1.05, 2.1 or 3.15 mg of pramipexole base ).

Excipients:

Tablets with a dosage of 0.375 mg: hypromellose 2208 - 112,500 mg; corn starch - 119.375 mg; carbomer 941-15,000 mg; silicon dioxide colloidal - 1,500 mg; magnesium stearate - 1,250 mg.

Tablets with a dosage of 0.75 mg: hypromellose 2208 - 148,500 mg; corn starch - 160,620 mg; Carbomer 941 16.500 mg; silicon dioxide colloidal - 1,980 mg; magnesium stearate - 1,650 mg.

Tablets with a dosage of 1.5 mg: hypromellose 2208 - 157,500 mg; corn starch - 169,650 mg; Carbomer 941 17.500 mg; silicon dioxide colloidal - 2,100 mg; magnesium stearate - 1,750 mg.

Tablets with a dosage of 3.0 mg: hypromellose 2208 - 191.250 mg; corn starch - 209,075 mg; carbomer 941-17,000 mg; silicon dioxide colloidal - 2,550 mg; magnesium stearate - 2,125 mg.

Tablets with a dosage of 4.5 mg: hypromellose 2208 - 225,000 mg; corn starch - 250,000 mg; carbomer 941-15,000 mg; silicon dioxide colloid - 3,000 mg; magnesium stearate - 2,500 mg.

Description:

Tablets with a dosage of 0.375 mg. White or almost white, round biconvex with bevelled edges of the tablet. On one side of the tablet, the engraving of the company's logo on the other side is engraved "P1".

Tablets with a dosage of 0.75 mg. White or almost white, round biconvex with bevelled edges of the tablet. On one side of the tablet, the engraving of the company's logo on the other side is engraved "P2".

Tablets with a dosage of 1.5 mg. White or almost white, oval biconvex tablets. On one side of the tablet, the engraving of the company's logo on the other side is engraving "RZ".

Tablets with a dosage of 3.0 mg. White or almost white, oval biconvex tablets. On one side of the tablet, the engraving of the company's logo on the other side is engraved "P4".

Tablets with a dosage of 4.5 mg. White or almost white, oval biconvex tablets. On one side of the tablet, the engraving of the company's logo on the other side is engraved "P5".

Pharmacotherapeutic group:dopamine receptor agonist

ATX: & nbsp

N.04.B.C.05 Pramipexole

Pharmacodynamics:

Pramipexole, a dopamine receptor agonist, with high selectivity and specificity binds to subgroup dopamine receptors D₂, of which the most pronounced affinity for D₃ receptors. Reduces the lack 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 arising 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 which an increase in the dose of MIAPEX® PD, prolonged-release tablets was performed faster than followed (every 3 days), up to 4.5 mg per day, there was an increase in blood pressure and heart rate. In studies on patients, this effect was not observed.

Pharmacokinetics:

Pramipexole is absorbed quickly and completely after ingestion. Absolute bioavailability exceeds more than 90% and the maximum concentration in plasma is reached approximately through 6 hours.As a rule, eating does not affect the bioavailability of pramipexole. After eating fatty foods, a slight increase is observed, approximately 20%, maximum concentration and deceleration, approximately 2 hour, time to reach the maximum concentration, not having clinical significance.

Pramipexole shows linear kinetics and a relatively small variability in plasma levels between patients, regardless of the pharmaceutical form.

Pramipexole binds to plasma proteins to a very small extent (<20%), and has a large volume of distribution (400 liters). There were high concentrations of the drug in the brain tissues of rats (approximately 8 times higher than in plasma).

It is exposed to a metabolism to an insignificant degree.

About 90% of the dose is excreted through the kidneys (80% unchanged) and less than 2% is detected in the stool. The total clearance of pramipexole is about 500 ml / min, the renal clearance is about 400 ml / min. Half-life (T_1/2) varies from 8 h from young to 12 h in the elderly.

Indications:

Symptomatic treatment of idiopathic Parkinson's disease.

The drug can be used for monotherapy or in combination with levodopa.

Contraindications:

Hypersensitivity to pramipexole or to any component of the drug.

Children under 18 years.

Carefully:

Renal failure, lowering blood pressure.

Pregnancy and lactation:

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

The possible effect of pramipexole on reproductive function was 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 given only if the potential benefit to the mother exceeds the potential risk to the fetus.

Excretion of the drug with breast milk has not been studied. The concentration of the drug in the milk of rats was higher than in plasma. Because the pramipexole inhibits the secretion of prolactin, we can assume that it also suppresses lactation. Therefore, the drug should not be taken during breastfeeding.

Effects on fertility in humans have not been studied. The results of studies conducted on animals do not indicate the presence of direct or indirect signs of adverse effects on fertility in males.

Dosing and Administration:

Tablets of prolonged action should be taken once a day, approximately at the same time of day. Swallow whole tablets, drinking water, the tablets should not be chewed, crush or grind. Tablets can be taken regardless of food intake.

If a dose of the drug is missed, then it should be taken if more than 12 hours have elapsed since the usual time of admission. If more than 12 hours, the missed dose should not be accepted, the next dose should be taken the next day at the usual time.

Patients who are already taking pills mirapex, can be translated into sustained-release tablets Mirapeks® PD during the day, at the same dose.

Initial therapy

As shown below, the dose should be gradually increased from the starting dose of 0,375 mg per day and then increased every 5-7 days. To prevent undesirable side effects, the dose should be selected until the maximum therapeutic effect is achieved.

Weeks	Dose (mg)	The total daily dose (mg)
1	0,375	0,375
2	0,75	0,75
3	1,50	1,50

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 per day.

Supportive 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 expanded stages of the disease, during the dose increase, the effectiveness of treatment was observed starting with a daily dose of 1.5 mg. This does not exclude that in individual patients doses above 1.5 mg per day can lead to an additional therapeutic effect.

These partially apply to patients with advanced stage of the disease, who were shown to reduce the dose of levodopa.

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. After that, the dose should be reduced by 0.375 mg per day.

Dose for patients receiving concomitant treatment with levodopa

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

Dose for patients with renal insufficiency

Excretion of pramipexole from the body depends on the function of the kidneys.

For initial therapy: in patients with creatinine clearance above 50 ml / min, a daily dose or frequency of reduction 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 carefully evaluated. If a further dose increase is necessary, the daily dose should be increased by 0.375 mg pramipexole at weekly intervals to a maximum dose of 2.25 mg pramipexole daily.

Data on the treatment with sustained-release tablets of patients with creatinine clearance below 30 mg / min are not available. One should study the expediency of using Mirapex tablets.

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

Dose for patients with hepatic impairment

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

Dose for children and adolescents

Safety and effectiveness of the drug in children and adolescents under the age of 18 years is not established.

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 overeating (hyperphagia), obsessive desire to shop (pathological shopping), hypersexuality and pathological craving for gambling; anomalous dreams, amnesia, heart failure, confusion, constipation, delirium, dizziness, dyskinesia, dyspnea, weakness, hallucinations, headache, hiccups, hyperkinesia, hyperphagia, lowering blood pressure, disturbing the secretion of antidiuretic hormone, insomnia, libido disorders, nausea, paranoia, peripheral edema; pneumonia; itching, rash and other hypersensitivity reactions; restlessness, drowsiness, sudden falling asleep, fainting, vision impairment (including diplopia, decreased visual acuity and clarity of perception), vomiting, weight loss, including decreased appetite.

The incidence of lowering blood pressure during treatment with Mirapex is not greater than with placebo. However, hypotension may occur in some patients at the beginning of treatment, especially if the dose is increased too quickly.

With the treatment with Mirapex, libido disorders (increase or decrease) can be associated.

Patients taking pramipexole tablets reported a sudden fall asleep during daytime activity, including driving, which sometimes led to traffic accidents. At the same time, some of them did not report having anxious signs such as drowsiness, often observed in patients taking pramipexole tablets at doses above 1.5 mg / day, which according to modern knowledge of the physiology of sleep always lead to sudden falling asleep . A clear connection with the duration of treatment was not revealed. At the same time, some patients took other drugs with potentially sedative properties. In most cases where such information was available, there were no such episodes after a dose reduction or discontinuation of treatment.

Patients with Parkinson's disease who received dopamine agonist therapy, including Mirapex, especially in high doses, reported a pathological craving for gambling, increased libido and hypersexuality, which usually occurred after lowering the dose or stopping treatment.

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

Inside the system-organ classes, the following categories are used for the incidence of side effects: very often (≥ 1/10); often (≥ 1/100, <1/10); infrequently (≥ 1 / 1,000, <1/100); rarely (≥ 1 / 10,000, <1 / 1,000); very rarely (<1 / 10,000); not installed.

System-Organic grade	By-effect	Frequency emergence
Infections and invasions	Pneumonia	Infrequently
Disorders from the endocrine system	Violation of the secretion of antidiuretic hormone	It is not known
Mental violations	Abnormal behavior (symptoms of impulsive and compulsive actions)	Often
	Abnormal dreams	Often
	Propensity to overeating	Infrequently
	Pathological Shopping	Infrequently
	Confusion of consciousness	Often
	Rave	Infrequently
	Hallucinations	Often
	Hyperphagia	Infrequently
	Hypersexuality	Infrequently
	Insomnia	Often
	Disorders of libido (increased libido, decreased libido)	Infrequently
	Paranoia	Infrequently
	Pathological craving for gambling	Infrequently
	Anxiety	Infrequently
Violations from side of the nervous systems	Amnesia	Infrequently
	Dizziness	Often
	Dyskinesia	Often
	Headache	Often
	Hyperkinesia	Infrequently
	Drowsiness	Often
	Sudden falling asleep	Infrequently
	Fainting	Infrequently
Vision disorders	Deterioration of vision (including diplopia, reduced visual acuity and clarity of perception)	Often
Violations from cardiovascular system	Reduction of blood pressure	Often
Violations from cardiovascular system	Heart failure	Not installed
Disturbances from the respiratory system	Dyspnea	Infrequently
Disturbances from the respiratory system	Hiccups	Infrequently
Infringements from gastrointestinal tract	Constipation	Often
	Nausea	Often
	Vomiting	Often
Infringements from skin and subcutaneous cellulose	Hypersensitivity reactions	Infrequently
	Itching	Infrequently
	Rash	Infrequently
Are common violations	Weakness	Often
Are common violations	Peripheral edema	Often
Reactions identified with special research	Decreased body weight, including decreased appetite	Often
Reactions identified with special research	Weight gain	Infrequently

Overdose:

Cases of severe overdose are not described.

Presumptive symptoms, characteristic of the pharmacodynamic profile of dopamine receptor agonists: nausea, vomiting, hyperkinesia, hallucinations, agitation and lowering of blood pressure.

Treatment: established antidote does not exist, overdosage recommended gastric lavage, symptomatic therapy, dynamic observation.

The effectiveness of hemodialysis is not established.

With signs of CNS excitation, the administration of neuroleptics is possible.

Interaction:

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 (eg, cimetidine), or which are themselves excreted through active secretion through the renal tubules, can interact with pramipexole, which is expressed in a decrease in the 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 such signs of excessivedopamine stimulation, like dyskinesia, agitation or hallucinations. In such 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. Anticholinergic drugs are mostly excreted by the metabolic pathway, so interaction with pramipexole is unlikely.

When the dose is increased in patients with Parkinson's disease, a dose reduction of levodopa is recommended, while the dose of other antiparkinsonian drugs should be maintained at a constant level.

Due to possible cumulative effects, patients should be cautioned when taking other sedative drugs or alcohol in combination with the Mirapex® PD drug, and also while taking medications that increase the concentration of pramipexole in plasma (eg, cimetidine).

Special instructions:

When prescribing Mirapex® PD to patients with renal insufficiency, a dose reduction is recommended, as described in the section "Method of administration and dose".

Hallucinations and confusion are known side effects when treated with dopamine agonists and levodopa.

Hallucinations are more common when treated with Mirapex® 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 can develop (primarily, visual). Patients should be warned that hallucinations affecting the ability to drive can be observed.

Patients and people who care about them should be aware that, in connection with the treatment of patients with dopaminergic agents, signs of abnormal behavior (symptoms of impulsive and compulsive actions), such as a tendency to overeating, an obsessive desire to shop (pathological shopping), may appear, Hypersexuality and pathological craving for gambling.In such cases, a decision to reduce the dose / phase-out of treatment should be considered.

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

It is recommended to check eyesight at regular intervals or immediately after prescribing the drug in the presence of such disorders.

Care should be taken when a patient has a serious cardiovascular disease. In connection with 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 about a possible sedative effect of the drug, including drowsiness and sudden falling asleep during daytime activities. Patients should be advised that in the event of increased drowsiness or episodes of sudden falling asleep during daytime activity (eg, talking, eating, etc.) that may happen at any time during treatment,they can not drive a car or engage in potentially dangerous activities, and a doctor should be consulted.

Epidemiological studies have shown that patients with Parkinson's disease have a high risk (from 2 before, approximately, 6 times higher) of melanoma than in the general population. Whether this increased risk is a consequence of Parkinson's disease, or is associated with other factors, such as taking medications that are used in Parkinson's disease, is not known.

Due to the reasons mentioned above, patients and those who care for them should be informed that during the period of receiving pramipexole or other dopaminergic medications need to be attentive to the possible development of melanoma.

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

Effect on the ability to drive transp. cf. and fur:

Patients should be informed of the possibility of hallucinations (mainly visual), which can affect the ability to drive a car.

When applying the drug, it is possible to develop sedative effects, including drowsiness and falling asleep during daily activities. Since drowsiness is a frequent undesirable phenomenon with potentially serious consequences, patients should not drive the car or work with other complex mechanisms until they have acquired sufficient experience with Mirapex® PD to assess whether it affects negatively or not on their mental and or motor activity. Patients should be advised that if during the treatment they experience increased drowsiness or episodes of falling asleep during their daily activities (i.e. during a conversation, eating, etc.), then they must give up driving, working with machinery, and see a doctor.

Form release / dosage:

Tablets of prolonged action, 0.375 mg, 0.75 mg, 1.5 mg, 3.0 mg, 4.5 mg.

Packaging:

10 tablets per blister from Al/Al.

1 or 3 blisters with instructions for use in a cardboard box.

Storage conditions:

Store in a dry place at a temperature of no higher than 25 ° C, out of the reach of children.

Shelf life:

3 years.

Do not use the product after the expiry date printed on the package.

Terms of leave from pharmacies:On prescription

Registration number:PL-000710

Date of registration:29.09.2011

The owner of the registration certificate:Boehringer Ingelheim International GmbHBoehringer Ingelheim International GmbH Germany

Manufacturer: & nbsp

BOEHRINGER INGELHEIM INTERNATIONAL, GmbH Germany

Representation: & nbspBERINGER INGELCHAIM INTERNATIONAL GmbH BERINGER INGELCHAIM INTERNATIONAL GmbH Germany

Information update date: & nbsp26.08.2015

Illustrated instructions

Instructions

Mirapex® PD (Mirapex® ER)