Pronoran® (Pronoran®)

Composition Pharmacodynamics Indications Carefully Contraindications Dosing and Administration Side effects Form release / dosage
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Active substancePiribedilPiribedil
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  • Prononkoling
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    ATOLL, LLC     Russia
  • Pronoran®
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    Servier Laboratories     France
    • Dosage form: & nbspControlled-release tablets coated with a coating.
    Composition:

    One tablet contains:

    Active substance: 50 mg of piribedil.

    Excipients: magnesium stearate 5.00 mg, povidone 20.00 mg, talc 130.00 mg. Sheath: carmellose sodium 0.71 mg, polysorbate 80 0.30 mg, dye crimson [Ponso 4 R] 3, 87 mg, povidone 6.31 mg, sodium hydrogen carbonate 0.15 mg, silicon dioxide colloid 0.27 mg, sucrose 57, 17 mg, talc 50.37 mg, titanium dioxide 0.78 mg, beeswax white 0.07 mg.

    Description:

    Round, biconvex tablets, covered with a shell, red. Allowed a slight heterogeneity of staining, glossiness and the presence of minor impregnations.

    Pharmacotherapeutic group:An antiparkinsonian remedy, including a dopaminergic drug.
    ATX: & nbsp

    N.04.B.C.08   Piribedil

    Pharmacodynamics:

    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, showing high affinity and selectivity for dopaminergic receptors such as D2 and D3.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, it exhibits antagonist activity of two main alpha-adrenergic receptors of the central nervous system (type a2A and a2C). Synergistic effect of pyribedil, as an antagonist a2 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 was 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 one compared with bromocriptine). The study involved 1103 patients of the 1-3 stages on the scale of Hen and Jahr (Hoehn & Jahr), 543 of whom received Pronoran.

    It was shown that Pronoran at a dosage of 150-300 mg / day 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, a statistically significant ratio of patients requiring emergency treatment with levodopa, who received piribedil (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).

    Pharmacokinetics:

    Piribedil quickly and almost completely absorbed from the gastrointestinal tract and is intensively distributed.

    The maximum concentration of pyribedil in the blood plasma is achieved 3-6 hours after oral administration of the controlled-release dosage form. The connection with 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.

    The plasma elimination of piribedil is two-phase in nature 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 the half-life (T1/2) of pyribedilum after intravenous administration averages 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 pyribedil is excreted by the kidneys in the form of metabolites.

    Indications:

    Auxiliary symptomatic therapy for chronic cognitive impairment and neurosensory deficit in the course of aging (attention, memory, etc.);

    Parkinson's disease:

    • monotherapy (with forms, mainly including tremor);
    • in combination therapy with levodopa at both the initial and later stages of the disease, especially in forms involving 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 (reduction of visual acuity, narrowing of the field of vision, reduction of contrast of colors, etc.).

    Contraindications:

    • Increased individual sensitivity to pyribedil and / or excipients included in the preparation.
    • Collapse.
    • Acute myocardial infarction.
    • Joint reception with neuroleptics (except for clozapine).
    • Children under 18 years of age (due to lack of data).

    Carefully: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:

    The drug is mainly used in elderly patients, whose pregnancy is unlikely. It was shown that in mice piribedil penetrates through the placental barrier and is distributed in the organs of the fetus.

    Due to the lack of data, the drug should not be used during pregnancy and during lactation.

    Dosing and Administration:

    Inside. The tablet should be taken after a meal, washed down with half a glass of water, without chewing.

    For all indications, except for Parkinson's disease: 50 mg (1 tablet) 1 time per day. In more severe cases: 50 mg twice a day.

    Parkinson's disease:

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

    Side effects:

    The reported adverse reactions with pyribedil are dose-dependent and are mainly associated with its dopaminergic activity. They are of a moderate nature, they occur mainly at the beginning of treatment and pass after the drug is discontinued.

    When taking the drug, the following adverse reactions may occur:

    From the gastrointestinal tract:

    Often (> 1/100, <1/10): minor gastrointestinal symptoms (nausea, vomiting, flatulence), these adverse reactions are reversible in the selection of the appropriate individual dose. Selection of a dose by gradually increasing the dosage (50 mg every two weeks until the recommended dose) leads to a significant decrease in the manifestation of these side effects.

    From the side of the central nervous system:

    Often (> 1/100, <1/10): there may be mental disorders such as confusion, hallucinations, agitation or dizziness that disappear when the drug is withdrawn.

    Taking pyribedil is accompanied by drowsiness and in extremely rare cases can be accompanied by pronounced drowsiness during the daytime until sudden falling asleep.

    From the cardiovascular system:

    Infrequently (> 1/1000, <1/100): hypotension, orthostatic hypotension with loss of consciousness or malaise or lability of blood pressure.

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

    In patients with Parkinson's disease who received dopamine agonist therapy, including piribedil, a tendency to gambling, increased libido and hypersexuality, obsessive desire to shop and compulsive overeating.

    Overdose:

    Symptoms: vomiting, which is due to its effect on the chemoreceptor trigger zone; lability of blood pressure (increase or decrease); dysfunction of the gastrointestinal tract (nausea, vomiting).

    Treatment: withdrawal of the drug, symptomatic therapy.

    Interaction:

    In connection with the mutual antagonism between dopaminergic antiparkinsonian drugs and neuroleptics, simultaneous administration with neuroleptics (with the exception of clozapine) is contraindicated.

    Patients with extrapyramidal syndrome, neuroleptic induced reception, therapy should be administered anticholinergic drugs and should not be administered dopaminergic antiparkinsonian drugs (because of dopaminergic receptor blocking neuroleptics).

    Dopaminergic antiparkinsonian agents may cause or exacerbate psychotic disorders. If you want the appointment of antipsychotic drugs in patients with Parkinson's disease receiving treatment with dopaminergic antiparkinsonian agents, the dose of the latter should be gradually reduced to the final abolition of (sudden cancellation of dopaminergic drugs linked to the risk of development of "neuroleptic malignant syndrome").

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

    co-administration of these drugs is not recommended due to the mutual antagonism between dopaminergic antiparkinsonian drugs and tetrabenazine.

    It is not recommended to use pyribedil together with alcohol.

    Care should be taken when prescribing piribedil with other drugs that have a sedative effect.

    Special instructions:

    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. This phenomenon is extremely rare, but nevertheless, patients who drive a car and / or work on equipment requiring a high degree of attention must be warned about this. If such reactions occur, consider lowering the dose of piribedil or discontinuing therapy with this drug.

    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.

    Patients and their caregivers should be warned about possible symptoms of behavioral disorders (gambling addiction, increased libido and hypersexuality, obsessive desire to shop and compulsive overeating) when taking the drug.If such symptoms occur, consider lowering the dose or gradually stopping therapy with the drug.

    Dye crimson, which is part of the drug, in some patients increases the risk of allergic reaction.

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

    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.

    Form release / dosage:

    Controlled-release tablets coated with a coating, 50 mg each.

    Packaging:

    For 15 tablets per blister (PVC / Al). Two blisters with instructions for medical use in a pack of cardboard.

    30 tablets per blister (PVC / Al). 1 blister with instructions for medical use in a pack of cardboard.

    When packaging (packing) in the Russian company, LLC "Serdiks" is placed on 30 tablets in a blister (PVC / Al), 1 blister with instructions for use in a pack of cardboard.

    Storage conditions:

    Special storage conditions are not required.

    Keep out of the reach of children.

    Shelf life:

    3 years.

    Do not use at the end of the expiration date printed on the package.

    Terms of leave from pharmacies:On prescription
    Registration number:П N015516 / 01
    Date of registration:25.12.2008
    The owner of the registration certificate:Servier LaboratoriesServier Laboratories France
    Manufacturer: & nbsp
    Representation: & nbspServier Laboratories Servier Laboratories France
    Information update date: & nbsp18.10.2015
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