Barviton

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

Composition:

Active substance: vinpocetine;

1 ml of solution contains 5 mg of vinpocetine;

Excipients: ascorbic acid, sodium metabisulfite (E 223), tartaric acid, benzyl alcohol, sorbitol (E 420), water for injections.

Pharmaceutical form. Injection solution.

Main physicochemical properties: colorless or slightly greenish-colored transparent liquid.

Pharmacotherapeutic group. Psychostimulants and nootropic agents. ATC code N06BX18.

Pharmacological Properties.

Pharmacodynamics.

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

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

Cavinton 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 primary 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 guanosine monophosphate (cGMP) phosphodiesterase (PDE); increases levels of cAMP and cGMP in the brain. The drug increases ATP concentration and the ATP/AMP ratio; enhances turnover of noradrenaline and serotonin in the brain; stimulates the ascending noradrenergic system; possesses antioxidant activity. As a result of all these effects, vinpocetine exerts cerebroprotective action.

Cavinton improves microcirculation in the brain: the drug inhibits platelet aggregation, reduces pathologically elevated blood viscosity, increases erythrocyte deformability, and inhibits adenosine uptake, thereby improving oxygen transport in tissues by reducing the affinity of hemoglobin for oxygen.

Cavinton 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.

Distribution. In studies involving oral administration of the drug to 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. Radioactivity concentration in the brain did not exceed that in the blood.

In humans, plasma protein binding is 66%. Absolute oral bioavailability of vinpocetine is 7%. The volume of distribution is 246.7±88.5 L, indicating extensive tissue binding. The value of vinpocetine clearance (66.7 L/hour) exceeds hepatic plasma flow (50 L/hour), 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. Elimination half-life in humans is 83±1.29 hours. In studies using radiolabeled compound, the main route of elimination was found to be via urine and feces in a ratio of 60:40. A greater amount of radiolabeled compound was detected in bile in rats and dogs, but significant enterohepatic circulation was not observed. Apovincaminic acid is excreted by the kidneys via simple glomerular filtration; the elimination half-life of this metabolite 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 25–30%. After oral administration, the area under the curve (AUC) of AVA is twice as high compared to 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, the amount of unchanged vinpocetine excreted was only a few percent of the administered dose.

An important and significant property of vinpocetine is the lack of need for dose adjustment in patients with liver or kidney disease, due to its metabolic pathway and absence of accumulation.

Changes in pharmacokinetic properties under special conditions (e.g., age, concomitant diseases). Since Cavinton is primarily indicated for the 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 pharmacokinetic studies 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, 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 (e.g., thrombosis, obstruction of the central retinal artery or vein).

Otorhinolaryngology. For the treatment of age-related hearing loss in acute vascular pathology, toxic (drug-induced) damage, or damage of other origins (idiopathic, due to noise exposure), Meniere's disease, and tinnitus.

Contraindications.

Acute phase of hemorrhagic cerebral stroke, severe ischemic heart disease, severe forms of arrhythmia.

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

Interaction with other medicinal products and other forms of interaction.

During clinical studies, no interactions were observed when vinpocetine was administered concomitantly with β-blockers (clonolol, pindolol), clomethiazole, glibenclamide, digoxin, acenocoumarol, or hydrochlorothiazide. In isolated cases, a slight additive effect was observed when vinpocetine was used concomitantly with α-methyldopa; therefore, regular monitoring of blood pressure is required when this combination of drugs is used.

Despite the lack of clinical data confirming possible interactions, caution is recommended when co-administering vinpocetine with drugs affecting the central nervous system, antiarrhythmic agents, anticoagulants, and fibrinolytic agents.

Special precautions for use

Due to the presence of benzyl alcohol (20 mg in 2 ml), hypersensitivity reactions may occur.

Due to the presence of sodium metabisulfite, the drug may cause severe allergic reactions and bronchospasm.

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

ECG monitoring is recommended in patients with QT interval prolongation syndrome or when concomitantly using medicinal products that may prolong the QT interval.

The drug contains a small amount of sorbitol; therefore, in patients with diabetes mellitus, blood glucose levels should be monitored periodically during treatment.

In case of fructose intolerance or fructose-1,6-diphosphatase deficiency in the patient, the use of this drug should be avoided.

Use during pregnancy or breastfeeding

Use of the drug during pregnancy or breastfeeding is contraindicated.

Pregnancy. Vinpocetine crosses the placental barrier, but concentrations detected in the placenta and fetal blood are lower than in maternal blood. No teratogenic or embryotoxic effects have been observed. In animal studies, administration of high doses of vinpocetine was associated in some cases with placental hemorrhage and abortion, primarily due to enhanced placental circulation.

Breastfeeding. Vinpocetine passes into breast milk. In studies using radiolabeled vinpecetine, radioactivity in breast milk was ten times higher than in maternal blood. The amount excreted into milk within 1 hour amounts to 0.25% of the administered dose. Since vinpocetine is excreted into breast milk and there are no data on its effects on the newborn, the use of vinpocetine during breastfeeding is contraindicated.

Ability to influence reaction rate when driving or operating machinery

There are no data regarding the effect of the drug on the ability to drive vehicles or operate machinery. However, if adverse effects such as dizziness, weakness, or other central nervous system disturbances occur, it is recommended to refrain from such activities.

Method of Administration and Dosage

Administer only intravenously as a slow infusion (infusion rate should not exceed 80 drops/minute).

The drug must not be administered subcutaneously, intramuscularly, or intravenously in concentrated form.

The initial daily dose for adults is generally 20 mg in 500 ml of infusion solution. This dose may be increased up to 1 mg/kg body weight per day over 2–3 days, depending on the patient's tolerance to the drug.

The average duration of treatment is 10–14 days; the usual daily dose is 50 mg/day (50 mg in 500 ml of infusion solution), calculated for a body weight of 70 kg.

After completion of the infusion therapy course, it is recommended to continue treatment with Vinpocetine tablets.

Barviton for injection solution can be diluted with 0.9% sodium chloride solution or infusion solutions containing glucose. The prepared Barviton solution must be used within 3 hours after preparation.

Dosage adjustment is not required for patients with renal or hepatic impairment.

Children

The drug is contraindicated in children.

Overdose

Cases of overdose have not been reported.

Based on literature data, administration of the drug at a dose of 1 mg/kg body weight may be considered safe. Since there are no data on the use of doses exceeding this amount, administration of higher doses is not permitted.

In case of overdose, the following may occur: arterial hypotension, drowsiness, nausea, vomiting.

Treatment is symptomatic.

Adverse reactions.

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

Immune system disorders: hypersensitivity.

Metabolism and nutrition disorders: hypercholesterolemia, diabetes mellitus; anorexia.

Psychiatric disorders: euphoria, anxiety, agitation; depression.

Nervous system and sensory organ disorders: headache, dizziness, hemiparesis, somnolence; tremor, loss of consciousness, pre-syncopal state, weakness, hot flushes.

Eye disorders: hyphema, hypermetropia, decreased visual acuity, myopia; conjunctival hyperemia, optic disc edema, diplopia.

Ear and labyrinth disorders: hearing impairment, hyperacusis, hypoacusis, vertigo; tinnitus.

Cardiac disorders: myocardial ischemia/infarction, angina pectoris, arrhythmia, bradycardia, tachycardia, extrasystoles, palpitations; heart failure, atrial fibrillation.

Vascular disorders: arterial hypotension, arterial hypertension, hot flushes; blood pressure fluctuations, thrombophlebitis, venous insufficiency.

Gastrointestinal disorders: abdominal discomfort, dry mouth, nausea; vomiting, hypersalivation.

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

General disorders: hot flushes; asthenia, chest discomfort, inflammation, thrombosis at injection site.

Investigations: decreased blood pressure; increased blood pressure, ST segment depression and QT interval prolongation, increased blood urea levels; increased lactate dehydrogenase levels, PR interval prolongation on ECG, ECG changes.

Shelf life.

3 years.

Storage conditions.

Store in the original packaging, out of reach of children, at a temperature not exceeding 30 °C.

Incompatibility.

Do not use solvents not specified in the section "Dosage and administration". Vinpocetine solution is chemically incompatible with heparin and its low molecular weight analogs; therefore, their co-administration in the same syringe is prohibited. However, simultaneous use of anticoagulants and vinpocetine is permitted.

Vinpocetine solution is chemically incompatible with infusion solutions containing amino acids; therefore, such solutions must not be used for dilution of the drug.

Packaging. 5, 10, or 100 ampoules per carton; or 5 ampoules per blister, 1 or 2 blisters per carton.

Prescription status.

Prescription only.

Manufacturer.

Private Joint-Stock Company "Lekhim-Kharkiv".

Manufacturer's address and location of its business activity.

36 Severin Pototskogo Street, Kharkiv, Kharkiv Region, 61115, Ukraine.