Pronoran, 50 mg, 30 pcs.

Active substance:

pyribedil 50 mg;

Excipients:

 magnesium stearate - 5 mg;

povidone - 20 mg;

talcum powder - 130 mg; 

Shell: 

sodium carmellose — 0.71 mg;

polysorbate 80-0.3 mg;

Ponceau crimson dye 4R - 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

Pronoran has an antiparkinsonian effect.

Pharmacodynamics

The active substance pyribedil is an agonist of dopaminergic receptors. It penetrates into the bloodstream of the brain, where it binds to the dopaminergic receptors of the brain, showing high affinity and selectivity for dopaminergic receptors such as D ₂  and D ₃ .

The mechanism of action of piribedil determines the main clinical properties of the drug for the treatment of Parkinson's disease at both the initial and later stages of the disease with an effect on all major motor symptoms.

Piribedil, in addition to acting on dopaminergic receptors, exhibits antagonist activity of the two main central nervous system α-adrenergic receptors (α _2A  and α _2C ). The synergistic effect of piribedil as an antagonist of α ₂ receptors and an agonist of dopaminergic receptors in the brain has been demonstrated in various animal models with Parkinson's disease: prolonged use of piribedil leads to the development of less pronounced dyskinesia than levodopa, with a similar efficacy with respect to reversible akinesia, concomitant Parkinson's disease.

During pharmacodynamic studies in humans, the excitation of cortical electrogenesis of the dopaminergic type was shown, both during waking 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, pyribedil has been shown to improve attention and alertness associated with cognitive tasks.

The effectiveness of Pronoran ^®  as monotherapy or in combination with levodopa in the treatment of Parkinson's disease was studied in three double-blind, placebo-controlled clinical trials (2 studies compared to placebo and one compared to bromocriptine). The studies involved 1103 patients of the 1-3rd stage according to the Hen and Yara scale (Hoehn & Jahr), 543 of whom received Pronoran ^® .

It is shown that Pronoran ^®  in a dosage of 150-300 mg / day is effective in treating all motor symptoms with a 30% improvement on a unified Parkinson's disease rating scale (UPDRS, part III - motor) for more than 7 months with monotherapy and 12 months in combination with levodopa. Improvement in the second part of the UPDRS scale - activity in everyday life - was evaluated at the same values.

In monotherapy, the statistically significant ratio of patients requiring emergency treatment with levodopa receiving pyribedil (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 pyribedil (increases blood flow in the vessels of the lower extremities).

Pharmacokinetics

Pyribedil is rapidly and almost completely absorbed from the gastrointestinal tract and is intensively distributed.

C _{max of}  pyribedil in blood plasma is reached 3–6 hours after oral administration of a controlled-release dosage form. Plasma protein binding is average (unbound fraction is 20–30%). Due to the low binding of pyribedil to plasma proteins, the risk of drug interaction when used with other drugs is low.

Plasma elimination of pyribedil is biphasic and consists of the initial phase and the second slower phase, leading to the maintenance of a stable concentration of pyribedil in the blood plasma for more than 24 hours.

During the combined pharmacokinetic analysis, it was shown that T _{1/2 of}  piribedil after iv administration is on average 12 hours and does not depend on the dose administered.

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.

• auxiliary symptomatic therapy in case of chronic cognitive impairment and sensorineural deficiency during aging (attention, memory, etc.);
• Parkinson's disease: monotherapy (in forms predominantly including tremor) and as part of combination therapy with levodopa in both the initial and later stages of the disease, especially in forms including 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);
• treatment of symptoms of ophthalmic diseases of ischemic genesis (decreased visual acuity, narrowed visual field, decreased color contrast, etc.).

• increased individual sensitivity to pyribedil and / or excipients that make up the drug;
• collapse;
• acute myocardial infarction;
• joint administration with antipsychotics (except clozapine);
• children under 18 years of age (due to lack of data).

With caution: due to the fact that the preparation contains sucrose, in patients with intolerance to fructose, glucose or galactose, as well as in patients with a deficiency of sucrose isomaltase (a rare metabolic disorder), the drug is not recommended.

From the digestive tract: minor gastrointestinal symptoms (nausea, vomiting, flatulence), these adverse reactions are reversible in the selection of the appropriate individual dose. Dose selection by gradually increasing the dosage (50 mg every 2 weeks until the recommended dose is achieved) leads to a significant reduction in the occurrence of these side effects.

From the side of the central nervous system: mental disorders, such as confusion, hallucinations, agitation or dizziness, which disappear when the drug is withdrawn, can be noted.

Reception of piribedil is accompanied by drowsiness and in extremely rare cases it can be accompanied by severe drowsiness in the daytime until the sudden falling asleep.

From the CCC: hypotension, orthostatic hypotension with loss of consciousness or malaise, or blood pressure lability.

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

Due to the mutual antagonism between dopaminergic antiparkinsonian drugs and antipsychotics, simultaneous administration with antipsychotics (with the exception of clozapine) is contraindicated.

1. Patients with extrapyramidal syndrome caused by the use of antipsychotics should be prescribed anticholinergic drugs and dopaminergic antiparkinsonian drugs should not be prescribed (due to the blocking of dopaminergic receptors by antipsychotics).

2. Dopaminergic anti-Parkinsonian drugs can cause or exacerbate psychotic disorders. If prescription of antipsychotics is required for patients with Parkinson's disease receiving treatment with dopaminergic antiparkinsonian drugs, the dose of the latter should be gradually reduced until they are completely canceled (sudden cancellation of dopaminergic drugs is associated with the risk of developing malignant antipsychotic syndrome).

3. Antiemetic antipsychotics (antiemetic drugs that do not cause extrapyramidal symptoms should be used).

Due to the mutual antagonism between dopaminergic antiparkinsonian drugs and tetrabenazine, the simultaneous administration of these drugs is not recommended.

The use of pyribedil in conjunction with alcohol is not recommended.

Caution should be exercised when prescribing pyribedil with other drugs that have a sedative effect.

Inside, after eating, without chewing, drinking 1/2 cup of water.

For all indications, except for Parkinson's disease - 50 mg (1 tablet) once a day. In more severe cases, 50 mg 2 times a day.

Parkinson's disease: monotherapy - from 150 to 250 mg (3 to 5 tablets) per day, it is recommended to divide into 3 doses; if necessary, take a drug in a dose of 250 mg, it is recommended to take 2 tablets of 50 mg in the morning and afternoon and 1 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 1 tablet (50 mg) every 2 weeks.

Symptoms: vomiting due to the action on the chemoreceptor trigger zone, blood pressure lability (increase or decrease), gastrointestinal tract dysfunction (nausea, vomiting).

Treatment: drug withdrawal, symptomatic therapy.

In some patients (especially in patients with Parkinson's disease), while taking piribedil, sometimes a state of severe drowsiness occurs up to and including sudden falling asleep. This phenomenon is extremely rare, but nevertheless, patients driving a car and / or working on equipment requiring a high degree of attention should be warned about this. If such reactions occur, it is necessary to consider reducing the dose of pyribedil or discontinuing therapy with this drug.

Given the age of the population receiving pyribedil therapy, the risk of falls that may be caused by sudden falling asleep, hypotension, or confusion should be considered.

Patients and their guardians should be warned of possible symptoms of a behavior disorder (addiction to gambling, increased libido and hypersexuality, an obsessive desire to shop and compulsive overeating). If such symptoms occur, it is necessary to consider the issue of reducing the dose or gradually stopping drug therapy.

Crimson dye, which is part of the drug, in some patients increases the risk of developing an allergic reaction.

Influence on the ability to drive vehicles and mechanisms. Patients who have episodes of severe drowsiness and / or sudden falling asleep during pyribedil therapy should refrain from driving vehicles and equipment requiring a high degree of attention until these reactions disappear.