Composition, form of production and packaging
Controlled-release tablets coated with a coat, red, round, biconvex; slight color heterogeneity, glossiness and minor inclusions are allowed.
piribedil 50 mg
Excipients: magnesium stearate - 5 mg, povidone - 20 mg, talc - 130 mg.
Shell: carmellose sodium 0.71 mg, polysorbate 80 0.30 mg, dye crimson (Ponso 4R) 3.87 mg, povidone 6.31 mg, sodium hydrogen carbonate 0.15 mg, silicon dioxide colloid 0.27 mg, sucrose 51.17 mg, talc 50.37 mg mg, titanium dioxide - 0.78 mg, beeswax white - 0.07 mg.
15 pcs. - blisters (2) - packs of cardboard.
29 pcs. - blisters (1) - packs of cardboard.
30 pcs. - blisters (1) - packs of cardboard.
INSTRUCTION FOR THE SPECIALIST.
Description of the drug approved by the manufacturer for the printed edition of 2017.
The active substance piribedil is an agonist of dopaminergic receptors. Penetrates into the bloodstream of the brain, where it binds to the dopaminergic receptors of the brain, exhibiting high affinity and selectivity for dopaminergic receptors such as D 2 and D 3 .
The mechanism of action of piribedil causes the main clinical properties of the drug for the treatment of Parkinson's disease both at the initial and later stages of the disease with exposure to all major motor symptoms. Piribedil, in addition to acting on the dopaminergic receptors, exhibits antagonist activity in two major ОІ-adrenoreceptors of the central nervous system (type 2 2A and 2 2C ).
The synergistic effect of pyribedil, as an antagonist? 2 receptor agonist and dopaminergic receptor agonist, has been demonstrated in various animal models with Parkinson's disease: prolonged use of pyribedil leads to less pronounced dyskinesia than levodopa, with similar efficacy against reversible akinesia, concomitant Parkinson's disease.
In the course of pharmacodynamic studies in humans, excitation of dopaminergic cortical electrogenesis, both during waking and during sleep, was demonstrated with the manifestation of clinical activity with respect to various functions controlled by dopamine. This activity was demonstrated using a behavioral or psychometric scale. It has been shown that in healthy volunteers, piribedil improves attention and vigilance 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 trials versus placebo and 1 study compared to bromocriptine). In the studies, 1103 patients from the 1-3 stages on the Hoehn and Jahr scale participated, 543 of which received Pronoran В® . It has been shown that in the dosage 150-300 mg / day, Pronoran is effective in all motor symptoms with a 30% improvement in the Unified Parkinson's Disease Assessment Scale (UPDRS) III part (motor) for more than 7 months with monotherapy and 12 months in combination with levodopa. The improvement of the "activity in daily life" part on the UPDRS II scale was evaluated in 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 placebo group (40.2%).
The presence of dopaminergic receptors in the vessels of the lower limbs explains the vasodilating effect of pyribedil (increases blood flow in the vessels of the lower extremities).
Suction and distribution
Piribedil is quickly and almost completely absorbed from the digestive tract and is intensively distributed.
The maximum concentration (C max ) of pyribedil in blood plasma is achieved 3 to 6 hours after oral administration of the controlled-release dosage form. Binding to plasma proteins is average (unbound fraction is 20-30%). In view of the low connectivity of pyribedil with plasma proteins, the risk of drug interaction when used with other drugs is low.
Piribedil is intensively metabolized in the liver and excreted mainly in the urine: 75% of the absorbed pyribedil is excreted by the kidneys in the form of metabolites.
The plasma elimination of piribedil is biphasic and consists of an initial phase and a second, slower phase, leading to a stable concentration of pyribedil in the blood plasma for more than 24 hours. In a combined pharmacokinetic analysis, it was shown that T 1/2 pyribedil after i / in the administration is an average of 12 hours and does not depend on the administered dose.
- as an auxiliary symptomatic therapy for chronic cognitive impairment and neurosensory deficit in the course of aging (attention, memory, etc.);
- Parkinson's disease in the form of monotherapy (in forms that primarily involve tremor) or as part of combined therapy with levodopa in both the initial and later stages of the disease, especially in forms involving tremor;
- as an auxiliary symptomatic therapy for intermittent claudication due to obliterating diseases of arteries of the lower limbs (stage 2 according to the classification of Lerish and Fontaine);
- therapy of symptoms of ophthalmic diseases of ischemic origin (including reduction of visual acuity, narrowing of the field of vision, reduction of contrast of colors, etc.).
Inside. The tablet should be taken after a meal, washed down 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 tab.) 1 time / day. In more severe cases - 50 mg 2 times / day.
With Parkinson's disease in the form of monotherapy, 150-250 mg / day (3-5 tablets / day) are prescribed, divided into 3 divided doses per day. If you need to take the drug in a dose of 250 mg, it is recommended to take 2 tablets. on 50 mg in the morning and in the afternoon and 1 tab. 50 mg in the evening.
When used in combination with drugs levodopa daily dose is 150 mg (3 tablets): it is recommended to divide into 3 divided doses.
When choosing a dose in case of its increase, it is recommended to titrate the dose, gradually increasing by 1 tab. (50 mg) every 2 weeks.
Discontinuation of treatment
A sharp cessation of therapy with a dopaminergic receptor agonist is associated with a risk of malignant neuroleptic syndrome. To avoid this, you should reduce the dose of piribedil gradually, until complete withdrawal.
Disorder of habits and drives
To avoid the risk of occurrence of disorders of habits and drives, the lowest effective dose of the drug should be given. If such symptoms occur, consideration should be given to reducing the dose or gradually stopping therapy with the drug (see section "Special instructions").
Patients with hepatic and / or renal insufficiency
Studies of the use of piribedil in this group of patients have not been conducted. In patients with hepatic and / or renal insufficiency, piribedil should be used with caution.
Children and teens
The efficacy and safety of piribedil in children and adolescents under 18 years of age has not been studied, and there is currently no data on the use of piribedil in this population. There are no well-founded indications for the use of piribedil in the pediatric population.
The reported adverse reactions in the use of pyribedil are dose-dependent and are mainly associated with its dopaminergic activity. Adverse reactions are mild, occur mainly at the beginning of treatment and pass after drug withdrawal.
The frequency of side effects of pyribedil is given in the following gradation: very often (? 1/10), often (? 1/100, <1/10), infrequently (? 1/1000, <1/100), rarely (? 1 / 10000, <1/1000), very rarely (<1/10000), the frequency, unspecified.
The following adverse reactions may occur when taking the drug.
From the psyche: often - there may be mental disorders, such as confusion, excitement, hallucinations (visual, auditory, mixed), disappearing when the drug is withdrawn; Unspecified frequency - aggression, psychotic disorders (delirium, delirium).
From the nervous system: often - dizziness, disappearing when the drug is withdrawn. Taking piribedil can be accompanied by drowsiness and in extremely rare cases - pronounced sleepiness during the daytime until sudden falling asleep (see section "Special instructions"); Unspecified frequency - dyskinesia (motor disorders).
From the cardiovascular system: infrequently - hypotension, orthostatic hypotension with loss of consciousness or malaise or lability of blood pressure.
From the gastrointestinal tract: often - minor gastrointestinal disorders (nausea, vomiting, flatulence), which can occur, especially when selecting the appropriate individual dose. Dose selection, by gradually increasing the dose (50 mg every 2 weeks until the recommended dose) leads to a significant decrease in the manifestation of these side effects.
Disorder of habits and drives: patients with Parkinson's disease who received dopamine agonist therapy, including piribedil, noted a pathological gambling addiction, increased libido and hypersexuality, an obsessive desire to shop and overeating / compulsive overeating (see section "Special instructions").
General disorders and disorders at the site of administration: an unspecified frequency - with the therapy of dopamine agonists, peripheral edema was reported.
Allergic reactions: the risk of developing allergic reactions to the scarlet dye, which is part of the drug.
- increased individual sensitivity to pyribedil and / or auxiliary substances included in the preparation;
acute myocardial infarction;
- joint reception with neuroleptics (except clozapine) (see section "Drug Interactions");
- Children under 18 years of age (due to lack of data).
Due to the fact that the composition of the drug includes sucrose, patients with intolerance to fructose, glucose or galactose, as well as patients with a deficiency of sucrose isomaltase (a rare metabolic disorder), the drug is not recommended.
PREGNANCY AND LACTATION
Studies in animals have not revealed direct or indirect negative effects on embryo and fetus development, labor activity and postnatal development.
It was shown that in mice, pyribedil penetrates the placental barrier and is distributed in the fetal organs.
Due to the lack of data, the drug is not recommended for use during pregnancy and in women with preserved reproductive potential, who do not use reliable contraceptive measures.
Due to the lack of data, the drug is not recommended for use during breastfeeding.
APPLICATION FOR CHILDREN
Contraindicated in children and adolescents under 18 years.
Sudden falling asleep
In some patients (especially in patients with Parkinson's disease) on the background of taking piribedil, a state of severe drowsiness sometimes suddenly occurs until sudden falling asleep. Sudden falling asleep during daily activity, in some cases unconscious or occurring without previous symptoms, is extremely rare, but, nevertheless, patients managing the car and / or working on equipment requiring a high degree of attention should be warned about this. If such reactions occur, patients should refuse to drive and / or work on equipment requiring a high degree of attention. In addition, consideration should be given to reducing the dose of piribedil or discontinuing therapy with this drug.
It is known that dopamine agonists disrupt the systemic regulation of blood pressure, which can lead to the development of orthostatic hypotension.
It is recommended to monitor blood pressure, especially at the beginning of treatment, due to the general risk of developing orthostatic hypotension associated with dopaminergic drugs.
Given the age of the population receiving pyribedyl therapy, the risk of falls that can be caused by sudden falling asleep, hypotension or confusion is accounted for.
Disorder of habits and drives
Patients should be monitored to detect the development of a behavioral disorder.
Patients and their caregivers should be warned about possible symptoms of behavioral disorders and addictions (gambling addiction, increased libido and hypersexuality, obsessive desire to do shopping and transmission / compulsive overeating) when taking dopamine agonists, incl. piribedil. If such symptoms occur, consider lowering the dose or gradually stopping therapy with the drug.
There were reported cases of behavioral disorders that were associated with such manifestations as confusion, agitation, aggression. If such symptoms occur, consider lowering the dose or gradually stopping therapy with the drug.
Dopamine agonists can cause or exacerbate psychotic disorders such as delirium, delirium and hallucinations (see "Drug Interactions"). If such symptoms occur, consider lowering the dose or gradually stopping therapy with the drug.
Dyskinesia (movement disorders)
In patients with advanced Parkinson's disease, levodopa preparations may cause dyskinesia at the beginning of titration of the dose of piribedil. In this case, reduce the dose of piribedil.
Malignant neuroleptic syndrome
Symptoms similar to malignant neuroleptic syndrome were reported with a sharp abolition of dopaminergic drugs (see section "Dosage regimen").
There was reported the occurrence of peripheral edema on the background of therapy with dopamine agonists. This should be taken into account when prescribing piribedil.
Dye crimson, which is part of the drug, in some patients increases the risk of allergic reactions.
Impact on the ability to drive vehicles and manage mechanisms
Patients with episodes of severe drowsiness and / or sudden falling asleep during piribedil therapy should refrain from managing vehicles and equipment requiring a high degree of attention until these reactions disappear.
Symptoms: vomiting, which is due to the action of pyribedil on the chemoreceptor trigger zone; lability of blood pressure (increase or decrease); abnormal function of the digestive tract (nausea, vomiting).
Treatment: withdrawal of the drug, symptomatic therapy.
Due to the mutual antagonism between dopaminergic antiparkinsonian drugs and neuroleptics, simultaneous administration with neuroleptics (with the exception of clozapine) is contraindicated (see section "Contraindications.")
Patients with an extrapyramidal syndrome caused by taking antipsychotics should be treated with anticholinergic drugs and dopaminergic antiparkinsonian drugs should not be prescribed (due to the blocking of dopaminergic receptors by neuroleptics).
Dopaminergic receptor agonists can cause or exacerbate psychotic disorders. If neuroleptics are prescribed for patients with Parkinson's disease who are treated with dopaminergic antiparkinsonian drugs, the dose of the latter should gradually decrease until the final withdrawal (sudden withdrawal of dopaminergic drugs is associated with a risk of developing a "neuroleptic malignant syndrome") (see "Special instructions").
Antiemetic antipsychotics: antiemetic drugs should be used that do not cause extrapyramidal symptoms.
Due to the mutual antagonism between dopaminergic antiparkinsonian drugs and tetrabenazine, simultaneous use of these drugs is not recommended.
The simultaneous use of pyribedil with alcohol is not recommended.
Care should be taken when using pyribedil with other drugs that have a sedative effect.
TERMS OF RELEASE FROM PHARMACY
The drug is released on prescription.
TERMS AND CONDITIONS OF STORAGE
The drug should be stored out of the reach of children. Special storage conditions are not required. Shelf life - 3 years. Do not use at the end of the expiration date printed on the package.