Vinpotropil, 5 mg+400 mg capsules 60 pcs

Pharmacodynamics

Vinpotropil is a combined drug. It has properties typical for a psychostimulant (Vinpocetine) and for a nootropic (Vinpocetine, Piracetam).

As a psychostimulant

It improves brain metabolism by increasing glucose and oxygen consumption by brain tissue. Increases resistance of neurons to hypoxia; enhances glucose transport to the brain through the blood-brain barrier; switches the process of glucose breakdown to a more energy-saving aerobic route; selectively blocks Ca2+-dependent phosphodiesterase; increases levels of adenosine monophosphate (AMP), cyclic guanosine monophosphate (cGMP) and adenosine triphosphate (ATP) of the brain. It enhances metabolism of brain noradrenaline and serotonin; stimulates ascending branch of noradrenergic system, has antioxidant effect.

Decreases platelet aggregation and increased blood viscosity; increases red blood cell elasticity and blocks red blood cell utilization of adenosine; helps increase red blood cell oxygen output. Increases cerebral blood flow; reduces cerebral vascular resistance without significant changes in the indices of the systemic circulation.

It does not have the effect of “stealing” and increases the blood supply, especially in the ischemic areas of the brain. It penetrates through the placental barrier.

As a nootropic agent

It has a positive effect on brain metabolic processes, slightly increases the concentration of ATP in the brain, increases the synthesis of ribonucleic acid and phospholipids, stimulates glycolytic processes, increases glucose utilization; it improves integrative activity of the brain, promotes memory consolidation, facilitates learning; it changes the speed of excitation distribution in the brain, improves microcirculation without having a vasodilator effect, inhibits activated platelet aggregation; has a protective effect in brain damage caused by hypoxia, intoxication, electric shock; increases alpha and beta activity, reduces delta activity in the electroencephalogram, reduces the severity of vestibular nystagmus; improves brain hemisphere connections and synaptic conduction in neocortical structures, increases mental alertness, increases cerebral blood flow; does not have sedative, psychostimulant effect.

The effect develops gradually.

It has a pronounced effect on the symptoms of initial manifestations of cognitive disorders of cerebral-vascular genesis in elderly and senile patients. It is recommended in psychogeriatric practice.

Pharmacokinetics

Vinpocetine

Absorption

After oral administration, it is rapidly absorbed from the gastrointestinal tract. Time of reaching maximum concentration (TCmax) in blood plasma is 1 hour. Absorption occurs mainly in the proximal parts of the gastrointestinal tract. During passage through the intestinal wall it is not metabolized.

Distribution

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

In humans, plasma protein binding is 66%, bioavailability when administered orally is 7%. The volume of distribution is 246.7-88.5 L, which indicates high tissue binding. Total clearance (66.7 l/h) exceeds hepatic blood flow rate (50 l/h), indicating extrahepatic metabolism.

Metabolism

The main metabolite is apovincaminate (ABA), which is 25-30% of the parent compound. The area under the curve “concentration – time” of ABA after oral administration is twice as large as that after intravenous administration of vinpocetine. Thus, vinpocetine is subject to a pronounced “primary passage” effect through the liver. Other metabolites include: hydroxyvinpocetine, hydroxy-AVA, ABA-dioxyglycinate and their conjugates (sulfates and/or glucuronides).

The excretion of unchanged vinpocetine is low (a few percent). When repeatedly administered in doses of 5 mg and 10 mg, the kinetics are linear, with equilibrium plasma concentrations of 1.2±0.27 and 2.1±0.33 ng/mL, respectively. The elimination half-life in humans is 4.8±1.29 h.

Extracted by the kidneys and through the intestine at a ratio of 60:40. In rats and dogs high radioactivity when administered radioactively labeled vinpocetine is found in bile, however, significant enterohepatic recirculation was noted.

Pharmacokinetics in special patient groups (age, comorbidities)

The pharmacokinetics of vinpocetine in elderly patients was found not to differ significantly from that in younger patients, there was no cumulation of the drug.

Piracetam

Absorption

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

After a single dose of 2 g of piracetam the maximum concentration (Cmax) is reached within 30 min and is 40-60 mcg/ml; after 2-8 h it is found in the cerebrospinal fluid.

Distribution

The volume of distribution (Vd) is about 0.6 l/kg. It does not bind with plasma proteins. Piracetam penetrates through the blood-brain and placental barriers, as well as hemodialysis membranes.

In animal studies, piracetam was found to selectively accumulate in cortical tissues, mainly in the frontal, parietal and occipital lobes, in the cerebellum and basal nuclei.

Metabolism

It is not metabolized.

The elimination half-life from blood (T1/2) is 4-5 h and 8.5 h from cerebrospinal fluid. The T1/2 lengthens in renal insufficiency.

Extracted unchanged by the kidneys. Renal excretion is almost complete (>95%) within 30 h. Total clearance of piracetam in healthy volunteers is 86 ml/min.

Indications

Chronic vascular diseases of the retina and the vasculature of the eye. Hearing loss of perceptive type, Meniere’s disease, tinnitus.

Active ingredient

Composition

1 capsule contains

the active ingredients:

excipients:

colloidal silicon dioxide 2.6 mg,

107.4 mg lactose monohydrate, 5 mg talc;

the composition of the hard gelatin capsule #0:

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

caps: titanium dioxide 0.4552 mg, azorubin dye 0.1896 mg, gelatin 37.2852 mg.

How to take, the dosage

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

The duration of treatment is 2-3 months.

The dose of the drug should be gradually reduced before withdrawal.

Interaction

Vinpocetine

According to the results of clinical studies, no drug interactions with β-adrenal blockers (pindolol), clomipramide, glibenclamide, digoxin, hydrochlorothiazide and acenocoumarol were found.

Methyldopa may increase the hypotensive effect of vinpocetine; therefore, systematic BP control is required with their concomitant use.

While no clinical data are available, concomitant use with agents affecting the central nervous system, anticoagulants, and antiarrhythmic agents should be used with caution.

Piracetam

Thyroid hormones

Concomitant use of piracetam and thyroid extract (triiodothyronine + thyroxine) has reported confusion, irritability and sleep disturbance.

Acenocoumarol

. According to a published blinded clinical trial in patients with recurrent venous thrombosis, piracetam at a dose of 9.6 g/day has no effect on the dose of acenocoumarol required to achieve an international normalized ratio 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 and Willebrand factor concentrations (VIII: C; VIII: vW: Ag; VIII: vW: RCo), and whole blood and plasma viscosity.

Pharmacokinetic interactions

The possibility of changes in the pharmacokinetics of piracetam under the influence of other drugs is low because 90% of piracetam is excreted unchanged in the urine.

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

At a concentration of 1422 mg/ml, minimal inhibition of CYP2A6 isoenzyme (21%) and WA4/5 (11%) was observed. However, the values of the inhibition constant (Ki) probably go far beyond the 1422 mg/ml concentration. Thus, metabolic interactions of piracetam with other drugs are unlikely.

Anticonvulsants

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

Alcohol

Concomitant administration with alcohol did not affect the plasma concentration of piracetam; when 1.6 g of piracetam was taken, the plasma concentration of ethanol was not altered.

Special Instructions

Contraindications

Side effects

Side effects are quite rare. Frequency gradation is defined as follows: very frequently (≥1/10), frequently (≥1/100 to < 1/10), infrequently (≥1/1000 to < 1/100), rarely (≥1/10000 to < 1/1000), very rarely (< 1/10000) and frequency is unknown (cannot be estimated from available clinical trial data).

Vinpocetine

Disorders of the blood and lymphatic system

Rare: leukopenia, thrombocytopenia.

very rarely: anemia, erythrocyte agglutination.

Immune system disorders

Very rare: hypersensitivity.

Metabolic and nutritional disorders

Infrequent: hypercholesterolemia

Rare: decreased appetite, anorexia, diabetes mellitus.

Mental disorders

Rarely: insomnia, sleep disturbance, agitation, restlessness.

Very rare: euphoria, depression.

Nervous system disorders

Infrequent: headache. Rare: dizziness, impaired taste, stupor, hemiparesis, somnolence, amnesia.

Very rare: tremors, spasms.

Visual impairment

Rare: edema of the optic disc

Very rare: conjunctival hyperemia.

Hearing and labyrinth disorders

Infrequent: vertigo.Rarely: hyperacusis, hypoacusis, tinnitus.

Cardiac disorders

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

very rarely: arrhythmia, atrial fibrillation.

Vascular disorders

Infrequent: arterial hypotension.

Rare: arterial hypertension, hot flashes, thrombophlebitis.

Very rare: fluctuations in blood pressure.

Gastrointestinal disorders

Infrequent: abdominal discomfort, dry mouth, nausea.

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

Very rare: dysphagia, stomatitis.

Skin and subcutaneous tissue disorders

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

Very rare: dermatitis.

General disorders and disorders at the site of administration

Rarely: asthenia, malaise.

Very rare: chest discomfort, hypothermia.

Impact on the results of laboratory and instrumental studies

Infrequent: decreased blood pressure. Rare: increased arterial blood pressure, increased concentration of triglycerides in serum, ST-segment depression on electrocardiogram, decrease/increase of eosinophils, impaired liver function tests.

very rarely: increase/decrease of leukocyte count, decrease of red blood cell count, decrease of thrombin time, weight gain.

Piracetam

Blood and lymphatic system disorders

Prevalence unknown: bleeding.

Immune system disorders

Prevalence unknown: anaphylactoid reactions, hypersensitivity.

Psychiatric disorders

Often: nervousness. Infrequent: depression. Frequent unknown: agitation, anxiety, confusion, hallucinations.

Nervous system disorders

Often: hyperactivity. Infrequent: drowsiness.

Frequent unknown: ataxia, balance disorders, worsening of the course of epilepsy, headache, insomnia, tremor.

Hearing and labyrinth organ side

Prevalence unknown: vertigo.

Gastrointestinal system disorders

Prevalence unknown: abdominal pain (including in the upper parts), diarrhea, nausea, vomiting.

Skin and subcutaneous tissue disorders

Prevalence unknown: angioedema, dermatitis, pruritus, urticaria.

Reproductive system disorders

Prevalence unknown: increased sexual desire

General disorders and disorders at the site of administration

Infrequent: Asthenia

Laboratory and instrumental findings

Often: increased body weight

Overdose

Symptoms: increased severity of side effects.

Treatment: gastric lavage, administration of activated charcoal, symptomatic therapy.

Pregnancy use

Vinpocetine

The use during pregnancy and during breastfeeding is contraindicated.

Pregnancy

Vinpocetine penetrates through the placenta, but the plasma concentration in the placenta and in the fetus is lower than in the mother. Teratogenic and embryotoxic effects were not detected. In animal studies, when administered in high doses, placental bleeding and abortions occurred (presumably due to increased placental blood flow).

Breastfeeding

Vinpocetine penetrates into breast milk. According to preclinical studies with radioactively labeled vinpocetine, the concentration in breast milk of newborn animals was 10 times higher than in the blood of the mother. In 1 hour, 0.25% of the administered dose penetrates into the milk.

Do not use while breastfeeding or breastfeeding should be discontinued during treatment with vinpocetine.

Piracetam

Pregnancy

There are no sufficient data on the use of piracetam during pregnancy. Animal studies have shown no direct or indirect effects on pregnancy, embryo/fetal development, labor, or postnatal development.

Piracetam penetrates the placental barrier. Plasma concentrations of piracetam in the newborn reach 70-90% of that in the mother. Piracetam should be administered during pregnancy only in exceptional cases if the benefit to the mother exceeds the potential risk to the fetus and the clinical condition of the pregnant woman requires piracetam treatment.

Breastfeeding

Piracetam penetrates into the breast milk. Piracetam should not be used during breastfeeding or breastfeeding should be stopped when treating with piracetam. When deciding whether to stop breastfeeding or to discontinue treatment with piracetam, the benefit of breastfeeding for the baby must be weighed against the benefit of therapy for the woman.