Vinpotropil (vinpocetine 5 mg, piracetam 400) 60 pcs.

1 capsule contains

active substances: 

• vinpocetine 5 mg, piracetam 400 mg;

Excipients: 

• silicon dioxide colloidal 2.6 mg, 

• lactose monohydrate 107.4 mg, talc 5 mg;

the composition of the capsule hard gelatin No. 0:

case: titanium dioxide 1.7421 mg, quinoline yellow dye 0.5226 mg, sunset sunset dye yellow 0.0233 mg, gelatin 55.782 mg;

cap: titanium dioxide 0.4552 mg, dye azorubine 0.1896 mg, gelatin 37.2852 mg.

Pharmacodynamics

Vinpotropil is a combined drug. It has properties characteristic of a psychostimulating agent (vinpocetine) and for a nootropic agent (vinpocetine, piracetam).

As a psychostimulant

Improves brain metabolism, increasing glucose and oxygen consumption by brain tissue. Increases neuron resistance to hypoxia; enhances glucose transport to the brain, through the blood-brain barrier; transfers the process of glucose breakdown to an energetically more economical, aerobic path; selectively blocks Ca2 + -dependent phosphodiesterase; increases levels of adenosine monophosphate (AMP), cyclic guanosine monophosphate (cGMP), and adenosine triphosphate (ATP) in the brain. Enhances the metabolism of norepinephrine and serotonin in the brain; stimulates the ascending branch of the noradrenergic system, has an antioxidant effect. 

Reduces platelet aggregation and increased blood viscosity; increases the elasticity of red blood cells and blocks the utilization of adenosine by red blood cells; Reduces the return of oxygen by red blood cells. Increases cerebral blood flow; reduces the resistance of cerebral vessels without a significant change in systemic circulation. 

It does not have the effect of "robbing" and enhances blood supply, especially in ischemic areas of the brain. Penetrates through the placental barrier.

As a nootropic agent

It has a positive effect on metabolic processes of the brain, slightly increases the concentration of ATP in the brain, enhances the synthesis of ribonucleic acid and phospholipids, stimulates glycolytic processes, and enhances glucose utilization; improves integrative activity of the brain, promotes memory consolidation, facilitates the learning process; changes the speed of excitation propagation in the brain, improves microcirculation, without exerting a vasodilating effect, inhibits the aggregation of activated platelets; has a protective effect in case of brain damage caused by hypoxia, intoxication, electric shock; enhances alpha and beta activity, reduces delta activity on the electroencephalogram, reduces the severity of vestibular nystagmus; improves communication between the cerebral hemispheres and synaptic conduction in neocortical structures, increases mental activity, enhances cerebral blood flow; does not have a sedative, psychostimulating effect. 

The effect develops gradually.

It has a pronounced effect in relation to the symptoms of the initial manifestations of cognitive impairment of cerebrovascular origin in elderly and senile patients. Recommended in psycho-geriatric practice.

Pharmacokinetics

Vinpocetine

Absorption

After oral administration, it is rapidly absorbed from the gastrointestinal tract. The time to reach maximum concentration (TCmax) in blood plasma is 1 hour. Absorption occurs mainly in the proximal sections of the gastrointestinal tract. When passing through the wall of the intestine, it is not metabolized.

Distribution

Upon oral administration of radioactively labeled vinpocetine to rats, the highest concentrations were found in the liver and gastrointestinal tract. The maximum concentration in the tissues was observed 2-4 hours after administration. The concentration of radioactive labeled vinpocetine in the brain did not exceed the values ​​found in the blood.

In humans, the connection with plasma proteins is 66%, the bioavailability when taken orally is 7%. The volume of distribution is 246.7-88.5 L, which indicates a high binding to tissues. The total clearance (66.7 l / h) exceeds the rate of hepatic blood flow (50l / h), which indicates extrahepatic metabolism.

Metabolism

The main metabolite is apovincinnamate (ABA), comprising 25-30% of the starting compound. The area under the curve "concentration — time" of the ABA after oral administration is twice as large

such with the intravenous administration of vinpocetine. Thus, vinpocetine is susceptible to the pronounced effect of "primary passage" through the liver. Other metabolites include: hydroxyvinpocetine, hydroxy-ABA, ABA-dioxyglycinate and their conjugates (sulfates and (or) glucuronides).

Breeding

The excretion of unchanged vinpocetine is low (several percent). With repeated administration at doses of 5 mg and 10 mg, the kinetics is linear, the equilibrium plasma concentration is 1.2 ± 0.27 and 2.1 ± 0.33 ng / ml, respectively. The half-life of a person is 4.8 ± 1.29 hours. 

It is excreted by the kidneys and through the intestine in a ratio of 60:40. In rats and dogs, high radioactivity with the administration of radioactively labeled vinpocetine is found in bile, however, significant enterohepatic recirculation is noted.

Pharmacokinetics in special patient groups (age, concomitant diseases)

It has been revealed that the pharmacokinetics of vinpocetine in elderly patients does not significantly differ from that in young patients; there is no cumulation of the drug.

Piracetam

Absorption

After oral administration, piracetam is rapidly and almost completely absorbed from the gastrointestinal tract. Bioavailability is about 100%.

After a single dose of piracetam in a dose of 2 g, the maximum concentration (Cmax) is reached in 30 minutes and amounts to 40-60 μg / ml, after 2-8 hours it is found in the cerebrospinal fluid.

Distribution

The volume of distribution (Vd) is about 0.6 l / kg. Does not bind to plasma proteins. Piracetam crosses the blood-brain and placental barriers, as well as hemodialysis membranes. 

In an animal study, it was found that piracetam selectively accumulates in the tissues of the cerebral cortex, mainly in the frontal, parietal and occipital lobes, in the cerebellum and basal nuclei.

Metabolism

Not metabolized.

Breeding

The half-life from blood (T1 / 2) is 4-5 hours and 8.5 hours from cerebrospinal fluid. T1 / 2 lengthens with renal failure.

It is excreted unchanged by the kidneys. Excretion by the kidneys is almost complete (> 95%) within 30 hours. The total clearance of piracetam in healthy volunteers is 86 ml / min.

Chronic vascular diseases of the retina and choroid. Perceptual hearing loss, Meniere's disease, tinnitus.

Vinpocetine

Use during pregnancy and during breastfeeding is contraindicated.

Pregnancy

Vinpocetine crosses the placenta, but the plasma concentration in the placenta and the fetus is lower than that of the mother. Teratogenic and embryotoxic effects were not detected. In animal studies, administration of high doses resulted in placental bleeding and abortion (presumably due to an increase in placental blood flow).

Lactation

Vinpocetine passes into breast milk. According to preclinical studies with radioactively labeled vinpocetine, the concentration in breast milk of newborn animals was 10 times higher than that in maternal blood. For 1 h, 0.25% of the dose taken penetrates into the milk.

It should not be used during lactation or breast-feeding should be discontinued during treatment with vinpocetine.

Piracetam

Pregnancy

There are no sufficient data on the use of piracetam during pregnancy. Animal studies have not shown a direct or indirect effect on pregnancy, embryo / fetal development, childbirth or postnatal development.

Piracetam crosses the placental barrier. The plasma concentration of piracetam in newborns reaches 70-90% of that in the mother. Piracetam should be prescribed during pregnancy only in exceptional cases, if the benefit to the mother outweighs the potential risk to the fetus, and the clinical condition of the pregnant woman requires treatment with piracetam.

Breast-feeding

Piracetam passes into breast milk. Piracetam should not be used during breastfeeding or breast-feeding should be discontinued during treatment with piracetam. Upon acceptance

Decisions on the need to cancel breastfeeding or refuse treatment with piracetam should correlate the benefits of breastfeeding for the baby and the benefits of therapy for the woman.

Side effects are quite rare. Frequency gradation is defined as follows: very often (≥1 / 10), often (≥1 / 100 to <1/10), infrequently (≥1 / 1000 to <1/100), rarely (≥1 / 10000 to <1 / 1000), very rarely (<1/10000) and the frequency is unknown (it is impossible to estimate based on available data from clinical trials).

Vinpocetine

Disorders from the blood and lymphatic system

Rarely: leukopenia, thrombocytopenia.

Very rarely: anemia, red blood cell agglutination.

Immune System Impairment

Very rare: hypersensitivity.

Metabolic and nutritional disorders

Infrequently: hypercholesterolemia

Rarely: decreased appetite, anorexia, diabetes.

Mental disorder

Rarely: insomnia, sleep disturbance, agitation, restlessness.

Very rare: euphoria, depression.

Violation of the nervous system

Infrequently: headache. Rarely: dizziness, taste disturbance, stupor, hemiparesis, drowsiness, amnesia.

Very rarely: tremors, cramps.

Violation of the organ of vision

Rarely: swelling of the optic disc

Very rare: conjunctival hyperemia.

Violation of the organ of hearing and the labyrinth

Infrequently: vertigo. Rarely: hyperacusis, hypoacusia, tinnitus.

Heart disorder

Rarely: ischemia / myocardial infarction, angina pectoris, bradycardia, tachycardia, extrasystole, palpitations.

Very rare: arrhythmia, atrial fibrillation.

Violation of the vessels

Infrequently: arterial hypotension.

Rarely: arterial hypertension, hot flashes, thrombophlebitis.

Very rare: fluctuations in blood pressure.

Gastrointestinal Disorders

Infrequently: abdominal discomfort, dry mouth, nausea.

Rarely: abdominal pain, constipation, diarrhea, dyspepsia, vomiting.

Very rarely: dysphagia, stomatitis.

Violation of the skin and subcutaneous tissue

Rarely: erythema, excessive sweating, itching, urticaria, rash.

Very rare: dermatitis.

General disorders and disorders at the injection site

Rarely: asthenia, malaise.

Very rare: chest discomfort, hypothermia.

Influence on the results of laboratory and instrumental studies

Infrequently: lowering blood pressure. Rarely: an increase in blood pressure, an increase in the concentration of triglycerides in the blood serum, depression of the ST segment on the electrocardiogram, a decrease / increase in eosinophils, impaired functional liver tests.

Very rarely: an increase / decrease in the number of leukocytes, a decrease in the number of red blood cells, a decrease in thrombin time, an increase in body weight.

Piracetam

From the blood and lymphatic system

Frequency unknown: bleeding.

From the immune system

Frequency unknown: anaphylactoid reactions, hypersensitivity.

From the psyche

Often: nervousness. Infrequently: depression. Frequency unknown: agitation, anxiety, confusion, hallucinations.

From the nervous system

Often: hyperactivity. Infrequently: drowsiness.

The frequency is unknown: ataxia, imbalance, exacerbation of the course of epilepsy, headache, insomnia, tremor.

On the part of the organ of hearing and the labyrinth

Frequency unknown: vertigo.

From the digestive system

Frequency unknown: abdominal pain (including in the upper sections), diarrhea, nausea, vomiting.

On the part of the skin and subcutaneous tissue

Frequency unknown: angioedema, dermatitis, pruritus, urticaria.

From the reproductive system

Frequency unknown: increased sexual desire

General disorders and disorders at the injection site

Infrequently: asthenia

Laboratory Instrumentation

Often: weight gain

Vinpocetine

According to the results of clinical trials, drug interactions with β-blockers (pindolol), clomipramide, glibenclamide, digoxin, hydrochlorothiazide and acenocoumarol were not found.

Methyldopa can enhance the hypotensive effect of vinpocetine, therefore, their simultaneous use requires systematic monitoring of blood pressure.

Despite the lack of clinical data, simultaneous use with drugs that affect the central nervous system, anticoagulants and antiarrhythmics should be carried out with caution.

Piracetam

Thyroid hormones

With the simultaneous use of piracetam and thyroid extract (triiodothyronine + thyroxine), confusion, irritability and sleep disturbance were noted.

Acenocoumarol

According to a published blind clinical study in patients with recurrent venous thrombosis, piracetam at a dose of 9.6 g / day does not affect the dose of acenocumarol necessary to achieve an international normalized ratio of 2.5-3.5, but compared with the effects of acenocoumarol alone The addition of piracetam at a dose of 9.6 g / day significantly reduces platelet aggregation, β-thromboglobin release, fibrinogen concentration and von Willebrand factor (VIII: C; VIII: vW: Ag; VIII: vW: RCo), as well as whole blood viscosity and plasma.

Pharmacokinetic interactions

The possibility of changing the pharmacokinetics of piracetam under the influence of other drugs is low, since 90% of piracetam is excreted unchanged in the urine.

At concentrations of 142, 426 and 1422 mg / ml, piracetam does not inhibit isoenzymes of cytochrome P450 (CYP 1A2, 2B6, 2C8, 2C9, 2C19, 2D6, 2E1 and 4A9 / 11) in vitro.

At a concentration of 1422 mg / ml, minimal inhibition of the CYP2A6 isoenzyme (21%) and ZA4 / 5 (11%) was observed. However, the values ​​of the inhibition constant (Ki) probably go far beyond the concentration of 1422 mg / ml. Thus, metabolic interactions of piracetam with other drugs are unlikely.

Anticonvulsants

The administration of piracetam at a dose of 20 g / day for 4 weeks in patients with epilepsy who took constant doses of antiepileptic drugs (carbamazepine, phenytoin, phenobarbital and valproic acid) did not change their maximum and minimum concentrations.

Alcohol

Concomitant use with alcohol did not affect the concentration of piracetam in plasma; when taking 1.6 g of piracetam, the ethanol concentration in the plasma did not change.

For patients 18 years and older: inside, before meals, 1-2 capsules, 2-3 times a day. The last appointment is 4 hours before bedtime.

The duration of treatment is 2-3 months.

Before canceling, the dose of the drug should be gradually reduced.

Symptoms: increased severity of side effects.

Treatment: gastric lavage, intake of activated carbon, symptomatic therapy.