Piribedil composition. Medicinal reference book geotar. Neuroleptic malignant syndrome

"Piribedil" used in the treatment and/or prevention of the following diseases (nosological classification - ICD-10):

Gross formula: C16-H18-N4-O2

CAS code: 3605-01-4

pharmachologic effect

Pharmacology: Pharmacological action - antiparkinsonian. It is a dopamine receptor agonist. Stimulates dopamine receptors in the central nervous system, mainly in the nuclei of the extrapyramidal system. Increases blood supply to brain tissue, their oxygen consumption, and improves brain metabolism. Stimulates the transmission of nerve impulses, increases the electrical activity of cortical neurons (both during wakefulness and sleep). It excites peripheral dopamine receptors in vascular smooth muscle and has a vasodilating effect.

Rapidly absorbed from the gastrointestinal tract. C_max is reached after 1 hour, binding to plasma proteins is low. Biotransforms in the body to form two main metabolites. T_1/2 (biphasic) is 1.7-6.9 hours. It is excreted mainly by the kidneys (68% in the form of metabolites) and with bile (25%).

Indications for use

Application: Impaired cognitive functions and neurosensory deficits in the aging process; Parkinson's disease - monotherapy (for forms including tremor) or in combination with levodopa; “intermittent” claudication (obliterating arterial diseases); ischemic symptoms of ophthalmological diseases.

Contraindications

Contraindications: Hypersensitivity, arterial hypotension, collapse, myocardial infarction (acute phase), pregnancy, breastfeeding.

Use during pregnancy and breastfeeding: Contraindicated during pregnancy (adequate and well-controlled studies on use during pregnancy have not been conducted) and during breastfeeding.

Side effects

Side effects: Anxiety, excitement; orthostatic hypotension; nausea, vomiting, flatulence.

Interaction: Dopamine antagonists, incl. neuroleptics (phenothiazines, butyrophenones, thioxanthenes) and metoclopramide may reduce effectiveness (mutually).

Overdose: Symptoms: vomiting.

Treatment: symptomatic therapy.

Dosage and method of administration

Directions for use and dosage: Orally, after meals, 50 mg/day at a time, if necessary, 50 mg 2 times a day. Parkinson's disease: monotherapy - 150-250 mg/day in 3-5 doses; in combination with levodopa - 100-150 mg in 2-3 doses.

Precautions: In patients with elevated blood pressure, additional antihypertensive therapy is necessary.

In this article you can read the instructions for use of the drug Pronoran. Reviews of site visitors - consumers of this medicine, as well as the opinions of specialist doctors on the use of Pronoran in their practice are presented. We kindly ask you to actively add your reviews about the drug: whether the medicine helped or did not help get rid of the disease, what complications and side effects were observed, perhaps not stated by the manufacturer in the annotation. Analogues of Pronoran in the presence of existing structural analogues. Use for the treatment of Parkinson's disease, memory and attention disorders during aging in adults, children, as well as during pregnancy and lactation. Composition of the drug.

Pronoran- is an agonist of dopaminergic receptors. Penetrates into the bloodstream of the brain, where it binds to dopaminergic receptors of the brain, showing high affinity and selectivity for dopaminergic receptors of types D2 and D3.

The mechanism of action of piribedil (the active substance of the drug Pronoran) determines the main clinical properties of the drug for the treatment of Parkinson's disease both at the initial and later stages. late stages diseases affecting all major motor symptoms. Piribedil, in addition to its effect on dopaminergic receptors, exhibits the activity of an antagonist of two main alpha-adrenergic receptors of the central nervous system (type alpha2A and alpha2C).

The synergistic effect of piribedil as an alpha2 receptor antagonist and dopaminergic receptor agonist in the brain has been demonstrated in various animal models of Parkinson's disease: long-term use of piribedil leads to the development of less severe dyskinesia than levodopa, with similar effectiveness in relation to reversible akinesia, concomitant illness Parkinson's.

In the course of pharmacodynamic studies in humans, excitation of dopaminergic-type cortical electrogenesis was shown both upon awakening and during sleep, with the manifestation of clinical activity in relation to various functions, controlled by dopamine. This activity has been demonstrated using behavioral or psychometric scales. In healthy volunteers, piribedil has been shown to improve attention and vigilance related to 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 studies. clinical trials(2 studies compared with placebo and 1 study compared with bromocriptine). The studies involved 1103 patients of stages 1-3 according to the Hoehn & Jahr scale, 543 of whom received Pronoran. It has been shown that Pronoran at a dosage of 150-300 mg per day is effective in affecting all motor symptoms with a 30% improvement in the Unified Parkinson's Disease Rating Scale (UPDRS) part 3 (motor) for more than 7 months with monotherapy and 12 months in combination with Levodopa. Improvement of the "activity in" part Everyday life" on the UPDRS 2 scale was assessed at the same values.

With monotherapy, a statistically significant ratio of patients requiring emergency treatment There were fewer levodopa patients receiving piribedil (16.6%) than in the group of patients receiving placebo (40.2%).

Presence of dopaminergic receptors in blood vessels lower limbs explains the vasodilating effect of piribedil (increases blood flow in the vessels of the lower extremities).

Compound

Piribedil + excipients.

Pharmacokinetics

Pronoran is quickly and almost completely absorbed from the gastrointestinal tract and distributed intensively. The maximum concentration (Cmax) of piribedil in blood plasma is achieved 3-6 hours after oral administration dosage form with controlled release. Plasma protein binding is average (the unbound fraction is 20-30%). Due to the low binding of piribedil to plasma proteins, the risk drug interactions when used with other drugs, low. Piribedil is intensively metabolized in the liver and excreted mainly in the urine: 75% of absorbed piribedil is excreted by the kidneys in the form of metabolites. Plasma elimination of piribedil is biphasic and consists of an initial phase and a second more slow phase leading to the maintenance of a stable concentration of piribedil in the blood plasma for more than 24 hours.

Indications

  • as an auxiliary symptomatic therapy with chronic impairment of cognitive function and neurosensory deficits during the aging process (disorders of attention, memory, etc.);
  • Parkinson's disease in the form of monotherapy (in forms predominantly involving tremor) or as part of combination therapy with levodopa both in the initial and later stages of the disease, especially in forms including tremor;
  • as an auxiliary symptomatic therapy for intermittent claudication due to obliterating diseases of the arteries of the lower extremities (stage 2 according to the Leriche and Fontaine classification);
  • treatment of symptoms of ophthalmological diseases of ischemic origin (including decreased visual acuity, narrowing of the visual field, decreased color contrast).

Release forms

Controlled-release film-coated tablets 50 mg.

Instructions for use and dosage regimen

Inside. The tablet should be taken after meals with half a glass of water without chewing.

For all indications (except Parkinson's disease), the drug is prescribed in a dose of 50 mg (1 tablet) once a day. In more severe cases - 50 mg 2 times a day.

For Parkinson's disease, 150-250 mg per day (3-5 tablets per day) is prescribed as monotherapy, divided into 3 doses per day. If it is necessary to take the drug at a dose of 250 mg, it is recommended to take 2 tablets of 50 mg in the morning and afternoon and 1 tablet of 50 mg in the evening.

When used in combination with levodopa drugs, the daily dose is 150 mg (3 tablets): it is recommended to divide into 3 doses.

Stopping treatment

Abrupt discontinuation of dopaminergic agonist therapy is associated with a risk of developing neuroleptic malignant syndrome (NMS). To avoid this, the dose of Pronoran should be reduced gradually until complete withdrawal.

To avoid the risk of disorders of habits and desires, the lowest effective dose of the drug should be prescribed. If such symptoms occur, consider reducing the dose or gradually discontinuing drug therapy.

Patients with liver and/or kidney failure

No studies have been conducted on the use of Pronoran in this group of patients. In patients with hepatic and/or renal insufficiency, Pronoran should be used with caution.

Side effect

  • mental disorders such as confusion, agitation, hallucinations (visual, auditory, mixed), which disappear when the drug is discontinued;
  • aggression, psychotic disorders (delirium, delirium), dizziness, disappearing when the drug is discontinued;
  • drowsiness;
  • dyskinesia (motor disorders);
  • hypotension;
  • orthostatic hypotension with loss of consciousness or malaise or blood pressure lability;
  • minor gastrointestinal disorders (nausea, vomiting, flatulence), which may subside, especially when selecting the appropriate individual dose;
  • pathological addiction to gambling;
  • increased libido;
  • hypersexuality;
  • obsessive desire to shop;
  • overeating/compulsive overeating;
  • peripheral edema;
  • the risk of developing allergic reactions to the crimson dye included in the drug.

Contraindications

  • increased individual sensitivity to piribedil and/or excipients included in the drug;
  • collapse;
  • acute myocardial infarction;
  • concomitant use with antipsychotics (except clozapine);
  • children under 18 years of age (due to lack of data).

Use during pregnancy and breastfeeding

Fertility

Animal studies have not revealed direct or indirect negative effects of Pronoran on the development of the embryo and fetus, labor and postnatal development.

Pregnancy

In mice, piribedil has been shown to cross the placental barrier and distribute to fetal organs.

Due to the lack of data, the drug is not recommended for use during pregnancy and in women with preserved childbearing potential who do not use reliable contraceptive measures.

Breastfeeding period

Due to the lack of data, the drug is not recommended for use during breastfeeding.

Use in children

Contraindicated in children and adolescents under 18 years of age. The effectiveness and safety of Pronoran in children and adolescents under 18 years of age has not been studied, and there are currently no data on the use of piribedil in this population.

special instructions

Dispensed with a doctor's prescription.

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

Sudden falling asleep

In some patients (especially those with Parkinson's disease), while taking piribedil, a state of severe drowsiness sometimes suddenly occurs, even to the point of sudden falling asleep. Sudden falling asleep during daily activities, in some cases without awareness or without previous symptoms, is extremely rare, but nevertheless, patients driving a car and/or working on equipment requiring a high degree of attention should be warned about it. If such reactions occur, patients should refrain from driving and/or operating equipment that requires a high degree of attention. In addition, consideration should be given to reducing the dose of piribedil or discontinuing therapy with this drug.

Orthostatic hypotension

Dopamine agonists are known to disrupt systemic blood pressure regulation, which may result in orthostatic hypotension.

Given the age of the population receiving Pronoran therapy, the risk of falls, which may be caused by sudden sleep onset, hypotension or confusion, should be considered.

Disorder of habits and urges

Patients should be monitored for development of conduct disorder.

Patients and their caregivers should be warned about possible symptoms of behavioral and compulsive disorder (compulsive gambling, increased libido and hypersexuality, compulsive shopping and overeating/compulsive eating) when taking dopamine agonists, incl. piribedila. If such symptoms occur, consider reducing the dose or gradually discontinuing drug therapy.

Behavioral disorders

Cases of conduct disorder have been reported and have been associated with symptoms such as confusion, agitation, and aggression. If such symptoms occur, consider reducing the dose or gradually discontinuing drug therapy.

Psychotic disorders

Dopamine agonists may cause or worsen psychotic disorders such as delirium, delirium, and hallucinations. If such symptoms occur, consider reducing the dose or gradually discontinuing drug therapy.

Dyskinesia (motor disorders)

In patients with advanced Parkinson's disease while taking levodopa, dyskinesia may develop at the beginning of piribedil dose titration. In this case, the dose of piribedil should be reduced.

Neuroleptic malignant syndrome (NMS)

Neuroleptic malignant syndrome-like symptoms have been reported with abrupt discontinuation of dopaminergic medications.

Peripheral edema

Peripheral edema has been reported during dopamine agonist therapy. This should be taken into account when prescribing piribedil.

Excipients

The crimson dye included in the drug increases the risk of allergic reactions in some patients.

Impact on the ability to drive vehicles and operate machinery

Patients who have experienced episodes of severe drowsiness and/or sudden falling asleep during piribedil therapy should refrain from driving vehicles or equipment requiring a high degree of alertness until these reactions resolve.

Drug interactions

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

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

Dopaminergic receptor agonists may cause or worsen psychotic disorders. If the prescription of antipsychotics is required in patients with Parkinson's disease receiving treatment with dopaminergic antiparkinsonian drugs, the dose of the latter should be gradually reduced until permanent discontinuation (sudden withdrawal of dopaminergic drugs is associated with the risk of developing "neuroleptic malignant syndrome").

Antiemetic neuroleptics: Antiemetic drugs that do not cause extrapyramidal symptoms should be used.

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

Caution should be exercised when using piribedil with other drugs that have a sedative effect.

Analogues of the drug Pronoran

Structural analogues of the active substance:

  • Piribedil.

Analogs for therapeutic effect (drugs for the treatment of Parkinson's disease):

  • Azilect;
  • Benserazide;
  • Bromocriptine;
  • Duellin;
  • Zymox;
  • Izikom;
  • Cognitive;
  • Credanil;
  • Levodopa;
  • Madopar;
  • Mendylex;
  • Midantan;
  • Mirapex;
  • On whom;
  • Near;
  • Newpro;
  • Pantogam;
  • Pantogam asset;
  • Pantocalcin;
  • Parkon;
  • Permax;
  • PC Merz;
  • Pramipexole;
  • Requip Modutab;
  • Rolprina SR;
  • Segan;
  • Selegiline;
  • Sinemet;
  • Stalevo;
  • Tasmar;
  • Tremonorm;
  • Tropacin;
  • Phenotropil;
  • Cyclodol;
  • Eldepril;
  • Yumex.

If there are no analogues of the drug for the active substance, you can follow the links below to the diseases for which the corresponding drug helps, and look at the available analogues for the therapeutic effect.

Included in the preparations

Included in the list (Order of the Government of the Russian Federation No. 2782-r dated December 30, 2014):

VED

ONLS

ATX:

N.04.B.C.08 Piribedil

Pharmacodynamics:

Antiparkinsonian drug. The mechanism of action is associated with stimulation of dopamine receptors mainly in the nuclei of the extrapyramidal system. Increases blood supply to tissues and stimulates the transmission of nerve impulses, which helps improve brain metabolism.

It has a vasodilating effect due to its effect on dopamine receptors located in the smooth muscles of peripheral vessels. Pharmacokinetics:

After oral administration, it is quickly absorbed from the gastrointestinal tract, the maximum concentration is reached after 1 hour. Plasma protein binding is low. It is characterized by a high degree of metabolism with the formation of 2 main metabolites - hydroxylated and dehydroxylated. The concentration of piribedil in the blood plasma decreases in two phases - the half-life is from 1.7 hours to 6.9 hours. It is excreted mainly in the form of metabolites in the urine: by the kidneys - 68%, with bile - 25%.

 Indications: Parkinson's disease (both as monotherapy and in combination with levodopa), chronic cognitive impairment and neurosensory deficits (including attention and memory disorders) in senile dementia (as an additional symptomatic therapy), intermittent claudication due to occlusive diseases of the lower arteries limbs (as an additional therapy), ischemic circulatory disorders of the eye.

VI.G20-G26.G21 Secondary parkinsonism

VI.G20-G26.G20 Parkinson's disease

V.F00-F09.F01 Vascular dementia

V.F00-F09.F06.7 Mild cognitive impairment

VII.H53-H54.H53.4 Visual field defects

VII.H53-H54.H54.2 Decreased vision in both eyes

XVIII.R50-R69.R54 Old age

IX.I70-I79.I73.9 Peripheral vascular disease, unspecified

IX.I70-I79.I73.8 Other specified peripheral vascular diseases

Contraindications:

Acute myocardial infarction, acute vascular insufficiency, arterial hypotension, collapse, combined use with antipsychotics with pronounced antipsychotic properties (except clozapine), pregnancy, breastfeeding. Hypersensitivity to piribedil.

 Carefully:

When used in patients with arterial hypertension, simultaneous antihypertensive therapy is necessary.

Should not be used concomitantly with dopamine receptor antagonists. Pregnancy and lactation:

Contraindicated during pregnancy and breastfeeding. Category of action on the fetus according to FDA - not determined. There have been no adequate and well-controlled studies of the safety of piribedil during pregnancy.

Experimental studies have not established the teratogenic effect of piribedil. The drug is used mainly in older people when pregnancy is unlikely. Directions for use and dosage:

Orally after meals, 50 mg per day at a time, if necessary, 50 mg 2 times a day. Parkinson's disease: monotherapy - 150-250 mg per day in 3-5 doses; in combination with levodopa - 100-150 mg in 2-3 doses.

The frequency and duration of use depend on the indications, the patient's response to treatment, and the components of combination therapy.

 Side effects:

From the outside digestive system: rarely - nausea, vomiting, flatulence.

From the outside CNS: rarely - anxiety, agitation, drowsiness.

From the outside of cardio-vascular system: in some cases - orthostatic hypotension.

Mental disorders.

 Overdose:

Symptoms: vomit. Treatment: gastric lavage, symptomatic therapy.

 Interaction:

When used simultaneously with dopamine receptor antagonists, a mutual decrease in effectiveness is possible.

 Special instructions:

If it is necessary to use antipsychotics in patients with Parkinson's disease receiving, the dose of the latter should be reduced gradually until completely discontinued. Abrupt withdrawal of piribedil may cause neuroleptic malignant syndrome.

If indigestion occurs caused by taking piribedil, it is possible to prescribe antiemetic drugs that act on peripheral dopamine receptors (). Side effects from the gastrointestinal tract are reduced by individually selecting the dose or taking the drug strictly after the main meal. Indigestion occurs more often with individual predisposition and in the case of eating in between meals.

If severe drowsiness (even sudden falling asleep) occurs while taking piribedil, it is necessary to consider reducing the dose or discontinuing the drug.

 Instructions

Pharmacotherapeutic group N04BC08 - antiparkinsonian dopaminergic drugs.

Main Pharmacological action: piribedil is a dopaminergic receptor agonist, penetrates the blood-brain barrier and specifically binds to dopamine receptors in the brain, having a strong and specific affinity for D2 and D3 dopamine receptors; These features determine the effectiveness of the drug in reducing the main symptoms (rigidity, rest tremor, slowness of movements, akinesia) in the treatment of early and late stages of Parkinson's disease; the effect on dopaminergic (D2) receptors of peripheral and cerebral vessels, as well as stimulation by piribedil of the release of endothelial NO determines its vasodilatory effect effect that provides improvement in cerebral perfusion, glucose and oxygen utilization, as well as protection against neurodegeneration of ischemic origin that occurs during the aging process of the brain, unlike other dopamine agonists, piribedil is also an antagonist of two main α2-adrenergic receptors in the CNS (central nervous system) (α2A and α2C) thanks to this, piribedil effectively reduces symptoms that are resistant to treatment with levodopa (impaired gait, standing posture, impaired speech, facial expressions). The synergistic effect of piribedil as an α2-adrenergic receptor antagonist and dopamine agonist is also important for long-term use: treatment with piribedil causes less pronounced dyskinesia compared to levodopa, with similar effectiveness in eliminating manifestations of the akinetic form of parkinsonism; clinical studies have proven that the drug stimulates plug electrogenesis of the “dopaminergic” type both in wakefulness and during sleep, and also activates functions controlled by dopamine (mood, alertness, concentration, memory and other cognitive functions).

INDICATIONS: treatment of Parkinson's disease in monotherapy or in combination with levodopa, auxiliary symptomatic therapy for chronic disease. (Chronic) impairment of cognitive function and neurosensory deficits during brain aging in elderly patients (except Alzheimer's disease and other dementias.

Directions for use and dosage: prescribed for adults - treatment begins with 50 mg, the dose is increased gradually, by 50 mg every 2 weeks; Parkinson's disease - recommended doses for monotherapy: 150-250 mg / day in 3 doses in combination with levodopa - 150 mg / day, divided into 3 doses, other indications - 50 mg / day, if necessary, the dose can be increased to 100 mg / day daily, in 2 doses, taken after meals; the drug is prescribed for long-term use, the duration of treatment is determined individually.

Side effects when using drugs: mild nausea, vomiting, flatulence, confusion, hallucinations, agitation or dizziness, increased daytime sleepiness, with episodes of sudden falling asleep, arterial hypotension, orthostatic hypotension, fainting states or malaise, unstable blood pressure (blood pressure) AR (allergic reactions), including BA (bronchial asthma), especially in patients with an allergy to acetylsalicylic acid.

Contraindications to the use of drugs: hypersensitivity to piribedil or to any of the excipients; cardiovascular shock (Acute) phase of MI (myocardial infarction), in combination with antipsychotics (with the exception of clozapine).

Drug release forms: table (Tablets) film-coated, prolonged action, 50 mg.

Visamodia with other drugs

Do not use in combination with antipsychotics (except clozapine) due to antagonism between them. If antipsychotic medication is necessary for patients with Parkinson's disease taking piribedil, the dose should be reduced gradually until discontinuation to avoid worsening of symptoms (sudden withdrawal of dopaminergic drugs increases the risk of developing "neuroleptic malignant stimulant syndrome"). It is possible to use the drug in combination with antipsychotics that do not have extrapyramidal effects.

Features of use in women during pregnancy and lactation

Features of use for insufficiency of internal organs

Dysfunction of the cerebrovascular system: Contraindicated in cardiovascular shock, the (Acute) phase of myocardial infarction
Dysfunction of the liver:
Renal dysfunction No special recommendations
Respiratory system dysfunction: No special recommendations

Features of use in children and the elderly

Application measures

Information for the doctor: Contraindicated in cases of fructose intolerance, impaired absorption of glucose or galactose, or sucrase-isomaltase deficiency. Contains the dye cochineal red A (E 124), which may cause allergic reactions, including asthma, especially in patients with an allergy to acetylsalicylic acid.
Patient Information: It is not recommended to drive vehicles or work with potentially dangerous mechanisms until the side effects disappear.

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