Pronoran tablets p / o 50mg, No. 30

• Auxiliary symptomatic therapy for chronic impairment of cognitive function and neurosensory deficit during aging (disorders of attention, memory, etc.);

• Parkinson's disease:
  - monotherapy (in forms that mainly include tremor);
  - as part of combination therapy with levodopa, both in the initial and in the later stages of the disease, especially in forms that include tremor;

• As an auxiliary symptomatic therapy for intermittent claudication resulting from obliterating diseases of the arteries of the lower extremities (stage 2 according to the classification of Leriche and Fontaine);

• Therapy of symptoms of ophthalmic diseases of ischemic genesis (decreased visual acuity, narrowing of the visual field, decreased color contrast, etc.).

Inside. The tablet should be taken after meals, washed down with half a glass of water, without chewing.
For all indications, except for Parkinson's disease: 50 mg (1 tablet) once a day. In more severe cases: 50 mg twice daily.

Parkinson's disease:

• monotherapy: 150 to 250 mg (3 to 5 tablets) per day, divided into 3 doses per day. If you need to take the drug in a dose of 250 mg, it is recommended to take 2 tablets of 50 mg in the morning and afternoon and one tablet in the evening.

• in combination with levodopa preparations: 150 mg (3 tablets) per day, it is recommended to divide into 3 doses.

When selecting a dose, in case of its increase, it is recommended to titrate the dose, gradually increasing it by one tablet (50 mg) every two weeks.

One tablet contains:
Active ingredient: piribedil 50 mg.
Excipients: magnesium stearate 5.00 mg, povidone 20.00 mg, talc 130.00 mg.
Sheath: sodium carmellose 0.71 mg, polysorbate 80 0.30 mg, crimson dye [Ponso 4 R] 3.87 mg, povidone 6.31 mg, sodium bicarbonate 0.15 mg, colloidal silicon dioxide 0.27 mg, sucrose 57.17 mg, talc 50.37 mg, titanium dioxide 0.78 mg, white beeswax 0.07 mg.

• Increased individual sensitivity to piribedil and / or excipients that make up the drug.

• Collapse.

• Acute myocardial infarction.

• Joint reception with antipsychotics (except clozapine).

• Children under 18 years of age (due to lack of data).

With caution:
Due to the fact that the drug contains sucrose, patients with fructose, glucose or galactose intolerance, as well as patients with sucrosoisomaltase deficiency (a rare metabolic disorder) are not recommended to take the drug.

Tradename:

PRONORANЃ

International non-proprietary name:

Piribedil

Dosage form:

film-coated controlled release tablets.

COMPOSITION
One tablet contains:
Active substance: 50 mg piribedil.
Excipients: magnesium stearate 5.00 mg, povidone 20.00 mg, talc 130.00 mg.
Sheath: sodium carmellose 0.71 mg, polysorbate 80 0.30 mg, crimson dye [Ponso 4 R] 3.87 mg, povidone 6.31 mg, sodium bicarbonate 0.15 mg, colloidal silicon dioxide 0.27 mg, sucrose 57.17 mg, talc 50.37 mg, titanium dioxide 0.78 mg, white beeswax 0.07 mg.

DESCRIPTION
Red, round, biconvex film-coated tablets. Slight inhomogeneity of coloring, degree of glossiness and the presence of slight inclusions are allowed.

PHARMACOTHERAPEUTIC GROUP
Anti-Parkinsonian drug, including a dopaminergic drug.
ATX code: N04BC08

PHARMACOLOGICAL PROPERTIES
Pharmacodynamics
The active substance piribedil is an agonist of dopaminergic receptors.
Penetrates into the bloodstream of the brain, where it binds to dopaminergic receptors in the brain, exhibiting high affinity and selectivity for dopaminergic receptors such as D2 and D3. The mechanism of action of piribedil determines the main clinical properties of the drug for the treatment of Parkinson's disease, both in the initial and in the later stages of the disease, with an effect on all the main motor symptoms. Piribedil, in addition to acting on dopaminergic receptors, exhibits the activity of an antagonist of two main alpha-adrenergic receptors of the central nervous system (CNS) (type ?2A and ?2C).
The synergistic effect of piribedil as an antagonist of ? 2 receptors and an agonist of dopaminergic receptors in the brain has been demonstrated in various animal models with Parkinson's disease: long-term use of piribedil leads to the development of less pronounced dyskinesia than the use of levodopa, with similar efficacy in relation to reversible akinesia, a concomitant disease Parkinson's.
In the course of pharmacodynamic studies in humans, the excitation of cortical electrogenesis of the dopaminergic type was shown both upon awakening and during sleep with the manifestation of clinical activity in relation to various functions controlled by dopamine, this activity was demonstrated using a behavioral or psychometric scale. In healthy volunteers, piribedil has been shown to improve attention and alertness associated with cognitive tasks.
The efficacy of Pronoran as monotherapy or in combination with levodopa in the treatment of Parkinson's disease has been studied in three double-blind, placebo-controlled clinical trials (2 studies versus placebo and one versus bromocriptine). The study involved 1103 patients with stages 1-3 on the Hoehn & Jahr scale, 543 of whom received Pronoran. Pronoran at a dosage of 150-300 mg / day has been shown to be effective on all motor symptoms with a 30% improvement according to the Unified Parkinson's Disease Rating Scale (UPDRS) Part III (motor) for more than 7 months with monotherapy and 12 months in combination with levodopa. The improvement in the activity in daily life portion of the UPDRS II was rated the same.
With monotherapy, the statistically significant proportion of patients requiring emergency treatment with levodopa treated with piribedil (16.6%) was less than in the group of patients receiving placebo (40.2%).
The presence of dopaminergic receptors in the vessels of the lower extremities explains the vasodilating effect of piribedil (increases blood flow in the vessels of the lower extremities).

Pharmacokinetics
Piribedil is rapidly and almost completely absorbed from the gastrointestinal tract and is intensively distributed.
The maximum concentration of piribedil in blood plasma is reached 3-6 hours after oral administration of the controlled release dosage form.
The connection with plasma proteins is average (unbound fraction is 20-30%). Due to the low binding of piribedil to plasma proteins, the risk of drug interactions when used with other drugs is low.
Plasma elimination of piribedil is two-phase in nature and consists of an initial phase and a second slower phase, leading to the maintenance of a steady concentration of piribedil in blood plasma for more than 24 hours.
In the course of the combined pharmacokinetic analysis, it was shown that the half-life (t1 / 2) of piribedil after intravenous administration is on average 12 hours and does not depend on the administered dose.
Piribedil is extensively metabolized in the liver and excreted mainly in the urine: 75% of the absorbed piribedil is excreted by the kidneys as metabolites.

INDICATIONS

• Auxiliary symptomatic therapy for chronic impairment of cognitive function and neurosensory deficit during aging (disorders of attention, memory, etc.);

• Parkinson's disease:
  - monotherapy (in forms that mainly include tremor);
  - as part of combination therapy with levodopa, both in the initial and in the later stages of the disease, especially in forms that include tremor;

• As an auxiliary symptomatic therapy for intermittent claudication resulting from obliterating diseases of the arteries of the lower extremities (stage 2 according to the classification of Leriche and Fontaine);

• Therapy of symptoms of ophthalmic diseases of ischemic genesis (decreased visual acuity, narrowing of the visual field, decreased color contrast, etc.).

CONTRAINDICATIONS

• Increased individual sensitivity to piribedil and / or excipients that make up the drug.

• Collapse.

• Acute myocardial infarction.

• Joint reception with antipsychotics (except clozapine).

• Children under 18 years of age (due to lack of data).

With caution:
Due to the fact that the drug contains sucrose, patients with fructose, glucose or galactose intolerance, as well as patients with sucrosoisomaltase deficiency (a rare metabolic disorder) are not recommended to take the drug.

APPLICATION DURING PREGNANCY AND BREASTFEEDING
The drug is mainly used in elderly patients in whom pregnancy is unlikely. It has been shown that in mice, piribedil crosses the placental barrier and is distributed in the fetal organs.
Due to the lack of data, the drug should not be used during pregnancy and lactation.

DOSAGE AND METHOD OF APPLICATION
Inside. The tablet should be taken after meals, washed down with half a glass of water, without chewing.
For all indications, except for Parkinson's disease: 50 mg (1 tablet) once a day. In more severe cases: 50 mg twice daily.

Parkinson's disease:

• monotherapy: 150 to 250 mg (3 to 5 tablets) per day, divided into 3 doses per day. If you need to take the drug in a dose of 250 mg, it is recommended to take 2 tablets of 50 mg in the morning and afternoon and one tablet in the evening.

• in combination with levodopa preparations: 150 mg (3 tablets) per day, it is recommended to divide into 3 doses.

When selecting a dose, in case of its increase, it is recommended to titrate the dose, gradually increasing it by one tablet (50 mg) every two weeks.

SIDE EFFECTS The
noted side effects when taking piribedil are dose-dependent and mainly associated with its dopaminergic activity. They are moderate in nature, occur mainly at the beginning of treatment and disappear after discontinuation of the drug.
When taking the drug, the following side reactions may occur:
From the gastrointestinal tract:
Often (> 1/100, minor gastrointestinal symptoms (nausea, vomiting, flatulence), these side reactions are reversible when the appropriate individual dose is selected. by gradually increasing the dosage (50 mg every two weeks until the recommended dose is reached), leads to a significant reduction in the manifestation of these side effects.

From the side of the central nervous system:
Often (> 1/100, psychological disorders such as confusion, hallucinations, anxiety or dizziness, which disappear when the drug is
discontinued , may occur. Taking piribedil is accompanied by drowsiness and, in extremely rare cases, may be accompanied by severe drowsiness during the daytime up to before falling asleep suddenly.

On the part of the cardiovascular system:
It is extremely rare (hypotension, orthostatic hypotension with loss of consciousness or malaise or lability of blood pressure.

Allergic reactions: the risk of developing allergic reactions to the Crimson dye, which is part of the drug.

Patients with Parkinson's disease who received dopamine agonist therapy, especially while taking a high dose of the drug and in combination with levodopa, showed a tendency to gambling, increased libido and hypersexuality, these manifestations were mainly reversible with dose reduction or interruption of treatment.

OVERDOSE
Symptoms: vomiting due to its effect on the chemoreceptor trigger zone; lability of blood pressure (increase or decrease); dysfunction of the gastrointestinal tract (nausea, vomiting).
Treatment: drug withdrawal, symptomatic therapy.

INTERACTION WITH OTHER DRUGS
Contraindicated combinations of
antipsychotics (with the exception of clozapine)
Mutual antagonism between drugs used in the treatment of Parkinson's disease (antiparkinsonian drugs) and antipsychotics.
1. Patients with extrapyramidal syndrome caused by the use of antipsychotics should be prescribed therapy with anticholinergic drugs and should not be prescribed dopaminergic antiparkinsonian drugs (due to blocking of dopaminergic receptors by neuroleptics).
2. Patients with Parkinson's disease receiving treatment with dopaminergic antiparkinsonian drugs and requiring the appointment of antipsychotics should not continue taking levodopa due to increased manifestations of mental illness, as well as due to blocking of dopaminergic receptors by antipsychotics.
3. Antiemetic antipsychotics: antiemetic drugs that do not cause extrapyramidal symptoms should be used.

SPECIAL INSTRUCTIONS
In some patients (especially in patients with Parkinson's disease), while taking piribedil, a state of severe drowsiness sometimes suddenly occurs, up to sudden falling asleep. This phenomenon is extremely rare, but nevertheless, patients driving and / or working on equipment requiring a high degree of attention should be warned about it. If such reactions occur, it is necessary to consider reducing the dose of piribedil or discontinuing therapy with this drug.
The crimson dye, which is part of the drug, in some patients increases the risk of developing an allergic reaction.

FORM OF RELEASE
50 mg film-coated tablets with controlled release.
15 tablets per blister (PVC / Al). 2 blisters with instructions for medical use in a cardboard box.
30 tablets per blister (PVC / Al). 1 blister with instructions for medical use in a cardboard box.
When packing (packaging) at the Russian enterprise Serdix LLC, 30 tablets are placed in a blister (PVC / Al), 1 blister with instructions for use in a cardboard box.

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

STORAGE CONDITIONS No
special storage conditions are required.
Keep out of the reach of children.

RELEASE CONDITIONS
Prescription.