Barviton

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT BАRVITON (BARVITON)

Composition:

Active substance: vinpocetine;

1 tablet contains vinpocetine 5 mg (0.005 g);

Excipients: lactose monohydrate, potato starch, magnesium stearate, talc.

Pharmaceutical form. Tablets.

Main physicochemical properties: white or almost white tablets.

Pharmacotherapeutic group. Psychostimulants and nootropic agents. Vinpocetine.

ATC code N06B X18.

Pharmacological Properties

Pharmacodynamics

Vinpocetine is a compound with a complex mechanism of action that exerts beneficial effects on brain metabolism and improves cerebral blood flow, as well as enhances the rheological properties of blood.

Vinpocetine exhibits neuroprotective effects: the drug reduces the harmful effects of cytotoxic reactions caused by excitatory amino acids. It inhibits voltage-dependent Na⁺- and Ca²⁺-channels, as well as NMDA and AMPA receptors. Vinpocetine enhances the neuroprotective effect of adenosine.

Vinpocetine stimulates cerebral metabolism: the drug increases the uptake and utilization of glucose and O₂ by brain tissue. It enhances the brain's resistance to hypoxia; increases the transport of glucose—the exclusive energy source for the brain—across the blood-brain barrier; shifts glucose metabolism toward the more energetically favorable aerobic pathway; selectively inhibits Ca²⁺-calmodulin-dependent cyclic GMP phosphodiesterase (PDE); increases levels of cAMP and cGMP in the brain. The drug increases ATP concentration and the ATP/AMP ratio; enhances metabolism of norepinephrine and serotonin in the brain; stimulates the ascending noradrenergic system; possesses antioxidant activity. As a result of all the above-mentioned effects, vinpocetine exerts a cerebroprotective action.

Vinpocetine improves microcirculation in the brain: the drug inhibits platelet aggregation, reduces pathologically elevated blood viscosity, increases erythrocyte deformability, and inhibits adenosine uptake. It improves oxygen transport in tissues by reducing the affinity of O₂ to erythrocytes.

Vinpocetine selectively increases cerebral blood flow: the drug increases the cerebral fraction of cardiac output; reduces vascular resistance in the brain without affecting systemic circulation parameters (arterial pressure, cardiac output, pulse rate, total peripheral resistance); the drug does not cause a "steal effect." Moreover, under the influence of the drug, blood flow improves in damaged (but not yet necrotized) ischemic areas with low perfusion ("reverse steal effect").

Pharmacokinetics

Absorption: vinpocetine is rapidly absorbed, with maximum plasma concentration reached within 1 hour after oral administration. The primary site of vinpocetine absorption is the proximal segments of the gastrointestinal tract. The compound does not undergo metabolism during passage through the intestinal wall.

Distribution: in studies involving oral administration of the drug in rats, radiolabeled vinpocetine was found in the highest concentrations in the liver and gastrointestinal tract. Maximum tissue concentrations were observed 2–4 hours after drug administration. The concentration of radioactivity in the brain did not exceed that in the blood.

In humans: plasma protein binding is 66%. Absolute bioavailability of vinpocetine after oral administration is 7%. The volume of distribution is 246.7±88.5 L, indicating extensive tissue binding. The clearance value of vinpocetine (66.7 L/h) in plasma exceeds its hepatic clearance (50 L/h), suggesting extrahepatic metabolism of the compound.

Elimination: with repeated oral administration of the drug at doses of 5 mg and 10 mg, vinpocetine demonstrates linear kinetics; steady-state plasma concentrations are 1.2±0.27 ng/mL and 2.1±0.33 ng/mL, respectively. The elimination half-life in humans is 4.83±1.29 hours. Studies using radiolabeled compound have shown that the main excretion routes are via kidneys and intestine in a ratio of 60:40. A large amount of radiolabeled substance was found in bile in rats and dogs, but significant enterohepatic recirculation was not observed. Apovincaminic acid is excreted by the kidneys via simple glomerular filtration; the elimination half-life of this substance varies depending on the dose and route of vinpocetine administration.

Metabolism: the main metabolite of vinpocetine is apovincaminic acid (AVA), which is formed in humans at levels of 25–30%. After oral administration, the area under the plasma concentration-time curve (AUC) of AVA is twice that observed after intravenous administration, indicating AVA formation during presystemic metabolism of vinpocetine. Other identified metabolites include hydroxyvinpocetine, hydroxy-AVA, dihydroxy-AVA-glycinate, and their conjugates with glucuronides and/or sulfates. In each of the studied species, only a few percent of the administered dose was excreted unchanged.

An important and significant property of vinpocetine is the lack of need for dose adjustment in patients with liver or kidney disease, due to the drug's metabolism and absence of accumulation.

Changes in pharmacokinetic properties under special conditions (e.g., age, presence of concomitant diseases): since vinpocetine is primarily indicated for treatment of elderly patients, in whom changes in drug kinetics—such as reduced absorption, altered distribution and metabolism, and decreased elimination—are commonly observed, it was necessary to conduct studies evaluating the drug's kinetics specifically in this age group, especially during long-term use. Results of such studies demonstrated that the pharmacokinetics of vinpocetine in elderly individuals does not significantly differ from that in younger individuals, and no accumulation occurs. Standard doses of the drug can be used in patients with impaired liver or kidney function, as vinpocetine does not accumulate in these patients, allowing prolonged administration.

Clinical characteristics.

Indications.

Neurology. For the treatment of various forms of cerebrovascular pathology: conditions following stroke (cerebral circulation disorders), vertebrobasilar insufficiency, vascular dementia, cerebral atherosclerosis, post-traumatic and hypertensive encephalopathy. Helps reduce psychological and neurological symptoms in cerebrovascular pathology.

Ophthalmology. For the treatment of chronic vascular pathology of the choroid (vascular layer of the eye) and retina.

Otorhinolaryngology. For the treatment of age-related sensorineural hearing loss, Ménière’s disease, and tinnitus.

Contraindications.

Pregnancy and lactation period.

Hypersensitivity to the active substance or to any of the excipients.

The use of the medicinal product in children is contraindicated (due to the lack of clinical data).

Interaction with other medicinal products and other types of interactions.

Concomitant administration of vinpocetine with β-blockers (chloranolol, pindolol), clonamide, glybenclamide, digoxin, acenocoumarol, or hydrochlorothiazide in clinical studies was not accompanied by any interaction between them. Concomitant use of vinpocetine and α-methyldopa sometimes caused a slight enhancement of the hypotensive effect; therefore, regular monitoring of arterial pressure is necessary when this combination of drugs is used. Despite the absence of clinical data confirming possible interactions, caution is recommended when prescribing vinpocetine concomitantly with drugs affecting the central nervous system, as well as in cases of concomitant antiarrhythmic and anticoagulant therapy.

Special precautions for use

The presence of long QT syndrome and the use of drugs that may prolong the QT interval require periodic ECG monitoring.

In patients with increased intracranial pressure, arrhythmia or long QT syndrome, as well as when using antiarrhythmic drugs, therapy with this drug should be initiated only after careful assessment of the benefits and risks associated with its use.

The drug contains lactose and therefore should not be administered to patients with rare hereditary forms of galactose intolerance, lactase deficiency, or glucose-galactose malabsorption syndrome.

Fertility. No effect on fertility has been observed.

Teratogenic effect. No teratogenic effects have been observed.

Mutagenicity. Vinpocetine has no mutagenic activity.

Carcinogenicity. Vinpocetine has no carcinogenic effect.

Use during pregnancy or breastfeeding.

The use of the drug during pregnancy and breastfeeding is contraindicated.

Pregnancy: Vinpocetine crosses the placental barrier; however, the concentration of the drug in the placenta and fetal blood is lower than in the blood of the pregnant woman. Teratogenic effects of the drug have not been observed. In preclinical studies using high doses of the drug, placental bleeding and spontaneous abortion occurred in some cases, likely due to enhanced placental blood supply.

Breastfeeding: Vinpocetine is excreted into breast milk. In preclinical studies using a radioactive isotope, radioactivity in breast milk was 10 times higher than in the blood of adult animals. The use of vinpocetine during breastfeeding is contraindicated due to its excretion into breast milk and the lack of sufficient clinical data on the safety of the drug for nursing infants. Within one hour after a single dose of vinpocetine, 0.25% of the administered dose is excreted into breast milk.

Ability to influence reaction rate while driving or operating machinery.

There are no data on the effect of vinpocetine on the ability to drive or operate machinery. However, caution should be exercised due to the potential occurrence of somnolence, dizziness, and vertigo during treatment.

Method of Administration and Dosage.

Administer orally after meals. The daily dose for adults is 15–30 mg (5–10 mg three times a day). The duration of treatment is determined individually by the physician.

Dosage adjustment is not required for patients with kidney or liver disease.

Children.

The medicinal product should not be used in children (due to lack of clinical data).

Overdose.

Symptoms of overdose are unknown. According to scientific literature, a daily dose of 60 mg is considered safe. A single intake of 360 mg of vinpocetine was not accompanied by the development of any cardiovascular or other adverse effects.

Adverse reactions.

Blood and lymphatic system disorders: leukopenia, thrombocytopenia, anemia, erythrocyte agglutination.

Immune system disorders: hypersensitivity.

Metabolism and nutrition disorders: hypercholesterolemia, decreased appetite, anorexia, diabetes mellitus.

Psychiatric disorders: insomnia, sleep disorders, restlessness, excitement, euphoria, depression, agitation.

Nervous system disorders: headache, dizziness, dysgeusia, stupor, hemiparesis, somnolence, amnesia, tremor, seizures.

Eye disorders: optic disc edema, conjunctival hyperemia.

Ear and labyrinth disorders: vertigo, hyperacusis, hypoacusis, tinnitus.

Cardiac disorders: myocardial ischemia/infarction, angina pectoris, bradycardia, tachycardia, extrasystole, palpitations, arrhythmia, atrial fibrillation.

Vascular disorders: arterial hypotension, arterial hypertension, flushing, thrombophlebitis, blood pressure changes.

Gastrointestinal disorders: abdominal discomfort, dry mouth, nausea, abdominal pain, constipation, diarrhea, dyspepsia, vomiting, dysphagia, stomatitis.

Skin and subcutaneous tissue disorders: erythema, hyperhidrosis, pruritus, urticaria, rash, dermatitis.

General disorders: asthenia, weakness, feeling of warmth, chest discomfort, hypothermia.

Investigations: decreased blood pressure, increased blood pressure, increased blood triglyceride levels, ST segment depression on electrocardiogram, increased/decreased eosinophil count, changes in liver enzyme activity, increased/decreased white blood cell count, decreased red blood cell count, decreased prothrombin time, weight gain.

Shelf life. 5 years.

Storage conditions. Store in a place inaccessible to children, in the original packaging, at a temperature not exceeding 25 °C.

Packaging. 10 tablets per blister, 3, 5, 50, or 100 blisters per pack.

Prescription category. Prescription only.

Manufacturer. Private Joint-Stock Company "Lekhim-Kharkiv".

Manufacturer's address and place of business.
Ukraine, 61115, Kharkiv Oblast, Kharkiv, Severin Pototskoho Street, 36.