Pronoran

General characteristics. Structure:

Active agent: 50 mg of a piribedil.
Excipients: magnesium stearate, povidone, talc, karmelloza of sodium, polysorbate 80, dye crimson (Ponso 4 R), Natrii hydrocarbonas, silicon dioxide colloid, sucrose, titanium dioxide, white beeswax.
DESCRIPTION
Round, biconvex tablets, coated, red color. Insignificant heterogeneity of coloring, degree of glossiness and existence of insignificant impregnations is allowed.

Pharmacological properties:

Pharmacodynamics. Piribedit active agent is an agonist of dofaminergichesky receptors. Gets into a brain blood stream where contacts dofaminergichesky receptors of a brain, showing high affinity and selectivity in relation to dofaminergichesky receptors of the D2 and D3 type. The mechanism of action of a piribedil causes the main clinical properties of drug for treatment of a disease of Parkinson both on initial, and at later stages of a disease with impact on all main motor symptoms. Piribedil in addition to impact on dofaminergichesky receptors shows activity of the antagonist of two main alpha adrenergic receptors of the central nervous sitema (CNS) (type α2А and α2С). Synergy action of a piribedil as antagonist α2 receptors and an agonist of dofaminergichesky receptors of a brain it was shown on various animal models with Parkinson's disease: prolonged use of a piribedil leads to development of less expressed dyskinesia, than use of a levodopa, with similar efficiency in relation to the reversible akineziya accompanying Parkinson's disease.
During the pharmakodinamichesky researches at people initiation of cortical electrogenesis of dofaminergichesky type as was shown when awakening and during sleep with manifestation of clinical activity in relation to various functions controlled by dopamine, this activity was shown when using a behavioural or psychometric scale. It was shown that at healthy volunteers piribedit improves the attention and vigilance connected with cognitive tasks.
Pronoran's efficiency as monotherapy or in a combination with a levodopa at treatment of a disease of Parkinson was studied during three double - blind people - placebo - controlled clinical trials (2 researches in comparison with placebo and one in comparison with Bromocriptinum). 1103 patients of 1 - 3 stage on a scale Hen and Jara (Hoehn & Jahr) participated in researches, 543 of which received Pronoran.
It is shown that Pronoran in a dosage of 150 - 300 mg/days is effective at action on all motor symptoms from 30% improvement on the Unified Scale of Assessment of the Disease of Parkinson (UPDRS) III a part (motive) within more than 7 months at monotherapy
and 12 months in a combination with a levodopa. Improvement of a part "activity in everyday life" on a scale of UPDRS II was estimated in the same values.
At monotherapy piribedit statistically significant ratio of the patients needing the emergency treatment by a levodopa, receiving (16,6%) was less, than in group of the patients receiving placebo (40,2%).
Existence of dofaminergichesky receptors in vessels of the lower extremities explains the vasodilating action of a piribedil (increases a blood stream in vessels of the lower extremities).

Pharmacokinetics. Piribedil quickly and almost is completely absorbed from digestive tract and intensively distributed.
The maximum concentration of a piribedil in a blood plasma is reached in 3-6 hours after oral administration of a dosage form with controlled release. Communication with proteins of plasma average (the untied fraction makes 20-30%). Due to the low svyazyvayemost of a piribedil with proteins of plasma risk of medicinal interaction at use with other drugs low.
Plasma elimination of a piribedil has two-phase character and consists of the initial phase and the second slower phase leading to maintenance of steady concentration of a piribedil in a blood plasma within more than 24 hours.
During the combined pharmacokinetic analysis it was shown that the elimination half-life (t1/2) of a piribedil after intravenous administration averages 12 hours and does not depend on the entered dose.
Piribedil is intensively metabolized in a liver and brought mainly with urine: 75% of the absorbed piribedil are excreted by kidneys in the form of metabolites.

Indications to use:

• Auxiliary symptomatic therapy at chronic disturbance of cognitive function and neurosensory deficit in the course of aging (disorder of attention, memory, etc.).
• Parkinson's disease:
- monotherapy (at the forms which are preferential including a tremor);
- as a part of a combination therapy with a levodopa both on initial, and at later stages of a disease, especially at the forms including a tremor;
• As auxiliary symptomatic therapy at the alternating lameness arising owing to obliterating diseases of arteries of the lower extremities (the 2nd stage on classification of Leriche and Fontaine);
• Therapy of symptoms of ophthalmologic diseases of ischemic genesis (decrease in visual acuity, narrowing of a field of vision, contrast decrease of flowers, etc.).

Route of administration and doses:

Inside. The pill should be taken after food, to wash down with a half of a glass of water, without chewing.
According to all indications, except Parkinson's disease: on 50 mg (1 tablet) once a day. In more hard cases: 50 mg twice a day.
Parkinson's disease:
• monotherapy: from 150 to 250 mg (from 3 to 5 tablets) a day, having divided into 3 receptions a day. In need of administration of drug in a dose of 250 mg it is recommended to take 2 pill on 50 mg in the morning and in the afternoon and one tablet in the evening.
• in a combination with levodopa drugs: 150 mg (3 tablets) a day, it is recommended to divide into 3 receptions.
At selection of a dose in case of its increase it is recommended to titrate a dose, gradually increasing it by one tablet (50 mg) each two weeks.

Features of use:

Some patients (especially at patients with Parkinson's disease) against the background of reception of a piribedil sometimes suddenly have a condition of strong drowsiness up to sudden backfilling. This phenomenon is observed extremely seldom, but nevertheless, the patients driving the car and/or working at the equipment demanding high degree of attention have to be warned about it. At emergence of similar reactions it is necessary to consider a question of a dose decline of a piribedil or the termination of therapy by this drug.
Dye crimson, being a part of drug, at some patients increases risk of development of allergic reaction.

Side effects:

Noted side reactions at reception of a piribedil have dozozavismy character and are mainly connected with its dofaminergichesky activity. Have moderate character, meet mainly in an initiation of treatment and pass after drug withdrawal.
At administration of drug the following side reactions can meet:
From a gastro intestinal path:
Often (> 1/100, <1/10): insignificant gastrointestinal symptoms (nausea, vomiting, a meteorism), these side reactions have reversible character at selection of the corresponding individual dose. Selection of a dose, by gradually increase in a dosage (on 50 mg each two weeks before achievement of the recommended dose), leads to considerable decrease in manifestation of these side effects.
From TsNS:
Often (> 1/100, <1/10): psychological frustration, such as confusion of consciousness, a hallucination, the concern or dizzinesses disappearing at drug withdrawal can be noted.
Reception of a piribedil is followed by drowsiness and in extremely exceptional cases can be followed by the expressed drowsiness days up to sudden backfilling in the afternoon.
From cordial vascular system:
Extremely seldom (<1/10000): hypotension, orthostatic hypotension with a loss of consciousness or an indisposition or lability of arterial pressure.
Allergic reactions: risk of development of allergic reactions to dye Crimson, being a part of drug.
At the patients with Parkinson's disease receiving therapy by dopamine agonists, especially against the background of reception of a high dosage of drug and in a combination with a levodopa tendency to gamblings, strengthening a libido and hyper sexuality was noted, these manifestations were generally reversible at reduction of a dose or at treatment interruption.

Interaction with other medicines:

Contraindicated combinations
Neuroleptics (except for clozapine)
Mutual antagonism between the drugs used at treatment of a disease of Parkinson (protivoparkinsonichesky medicines) and neuroleptics
1. Patients with the extrapyramidal syndrome caused by reception of neuroleptics should appoint therapy anticholinergic medicines and it is not necessary to appoint dofaminergichesky protivoparkinsonichesky medicines (owing to blocking neuroleptics of dopaminergic receptors).
2. The patients with Parkinson's disease receiving treatment by dofaminergichesky protivoparkinsonichesky medicines, and demanding purpose of neuroleptics should not continue to accept a levodopa owing to strengthening of display of mental diseases, and also owing to blocking by neuroleptics of dopaminergic receptors.
3. Antiemetic neuroleptics: it is necessary to use the antiemetic drugs which are not causing extrapyramidal symptoms.

Contraindications:

• The increased individual sensitivity to the piribedil and/or excipients which are a part of drug.
• Collapse.
• Acute myocardial infarction.
• Joint reception with neuroleptics (except clozapine).
• Children's age up to 18 years (due to the lack of data).
With care:
Because sucrose, to patients with intolerance of fructose, glucose or galactose is a part of drug, and also patients with deficit of a sukrozoizomaltaza (rare disbolism) are not recommended to accept drug.
USE AT PREGNANCY AND FEEDING BY THE BREAST
Drug is generally used at elderly patients at whom emergence of pregnancy is improbable. It was shown that at mice piribedit gets through a placental barrier and it is distributed in bodies of a fruit.
Due to the lack of data drug should not be used during pregnancy and during feeding by a breast.

Overdose:

Symptoms: vomiting that is caused by its action on a hemoretseptorny trigger zone; lability of arterial pressure (increase or decrease); dysfunction of digestive tract (nausea, vomiting).
Treatment: drug withdrawal, symptomatic therapy.

Storage conditions:

PERIOD OF VALIDITY 3 years. Not to apply upon termination of the period of validity specified on packaging. Special storage conditions are not required. To store in the place, unavailable to children.

Issue conditions:

According to the recipe

Packaging:

Tablets with controlled release, coated, on 50 mg.
On 15 tablets in the blister (PVC / Is scarlet). On 2 blisters with the instruction on a medical use in a pack cardboard.
On 30 tablets in the blister (PVC / Is scarlet). On 1 blister with the instruction on a medical use in a pack cardboard.
When packaging (packaging) at the Russian enterprise LLC Serdiks place 30 tablets in the blister (PVC / Is scarlet), on 1 blister with the application instruction in a pack cardboard.