Vinpocetine

INSTRUCTION FOR MEDICAL USE OF THE MEDICINAL PRODUCT VINPOCETINE

Composition:

active substance: vinpocetine;

1 ml of the preparation contains 5 mg of vinpocetine;

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

Pharmaceutical form. Concentrate for solution for infusion.

Main physicochemical properties: colorless or slightly greenish clear liquid.

Pharmacotherapeutic group. Psychoanaleptics. Psychostimulants and nootropic agents. ATC code N06B X18.

Pharmacological Properties.

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

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

Vinpocetine stimulates cerebral metabolism: increases uptake and utilization of glucose and oxygen by brain tissue; enhances brain resistance to hypoxia; increases 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; elevates 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 the above-mentioned effects, vinpocetine exerts a cerebroprotective action.

Vinpocetine improves cerebral microcirculation: inhibits platelet aggregation, reduces pathologically elevated blood viscosity, increases erythrocyte deformability, and inhibits adenosine uptake, thereby improving oxygen delivery to tissues by reducing oxygen affinity to erythrocytes.

Vinpocetine selectively increases cerebral blood flow: 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); 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. It is known that radiolabeled vinpocetine reaches the highest concentrations in the liver and gastrointestinal tract. Maximum tissue concentrations are observed 2–4 hours after drug administration. Radioactivity concentration in the brain does not exceed that in 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 clearance value of vinpocetine (66.7 L/hour) exceeds hepatic and plasma values (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. The primary route of elimination is via urine and feces in a ratio of 60:40. No significant enterohepatic recirculation occurs. Apovincaminic acid is excreted by the kidneys through simple glomerular filtration; its elimination half-life 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 concentration-time curve (AUC) of AVA is twice higher than 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 studied species, only a few percent of the administered vinpocetine 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 its metabolism and absence of accumulation.

Changes in pharmacokinetic properties under special conditions (e.g., age, presence of concomitant diseases). Vinpocetine kinetics in elderly individuals do not significantly differ from those 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 such patients, allowing long-term treatment.

Clinical characteristics.

Indications.

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

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

Otorhinolaryngology. For the treatment of age-related hearing loss due to acute vascular pathology, toxic (drug-induced) injury, or injury of other nature (idiopathic, noise-induced), Meniere’s disease, and tinnitus.

Contraindications. Hypersensitivity to the active substance or to any of the excipients of the drug. Acute phase of hemorrhagic cerebral stroke, severe ischemic heart disease, severe forms of arrhythmia.

Interaction with other medicinal products and other types of interactions. No interactions were detected when vinpocetine was administered concomitantly with β-blockers such as chloranolol and pindolol, or with clopamide, glybenclamide, digoxin, acenocoumarol, or hydrochlorothiazide. In isolated cases, an additional effect was observed when α-methyldopa was used concomitantly with vinpocetine; therefore, regular monitoring of blood pressure is required when this combination is used. Caution is recommended when vinpocetine is used concomitantly with drugs affecting the central nervous system, as well as in cases of concomitant antiarrhythmic and anticoagulant therapy.

Special precautions for use

In patients with increased intracranial pressure, arrhythmia, or QT interval prolongation syndrome, as well as those receiving antiarrhythmic drugs, therapy with this medicinal product should be initiated only after careful assessment of the benefits and risks associated with its use.

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

The use of this medicinal product should be avoided in patients with fructose intolerance or fructose-1,6-diphosphatase deficiency.

The product contains sorbitol (E 420). If the patient has been diagnosed with intolerance to certain sugars, consultation with a physician is necessary before taking this medicinal product.

The product contains sodium metabisulfite (E 223), which may rarely cause hypersensitivity reactions and bronchospasm.

Use during pregnancy or breastfeeding. Vinpocetine is contraindicated during pregnancy and breastfeeding.

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

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

Ability to influence reaction speed while driving or operating machinery. There are no data on the influence of vinpocetine on the ability to drive or operate machinery; however, the possibility of somnolence, dizziness, and vertigo occurring during treatment should be taken into account.

Dosage and Administration

The drug is allowed to be administered only as a slow intravenous drip infusion! (The infusion rate must not exceed a maximum of 80 drops/minute).

The drug must not be administered intramuscularly or intravenously without dilution.

The initial daily dose for adults is 20 mg (2 ampoules) dissolved 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 of the drug.

The average duration of treatment course 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, continuation of treatment with Vinpocetine tablets is recommended.

The concentrate for infusion solution can be diluted with physiological saline or infusion solutions containing glucose (e.g., Salsole, Ringer, Rindex, Reomacrodex). The infusion solution should be used within 3 hours after preparation.

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

Children. The use of the drug in children is contraindicated (due to lack of data from appropriate clinical studies).

Overdose. Cases of overdose have not been reported. According to 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 the drug at doses exceeding this amount, administration at higher doses is not permitted.

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 disorders: headache, dizziness, hemiparesis, somnolence, tremor, loss of consciousness, hypotension, pre-syncope.

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, flushing, blood pressure fluctuations, venous insufficiency.

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

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

General disorders and administration site conditions: feeling of warmth, 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 level, increased lactate dehydrogenase level, PR interval prolongation on ECG, ECG changes.

Shelf life. 5 years.

Storage conditions. Store at temperatures not exceeding 25 °C in the original packaging.

Keep out of reach of children.

Incompatibilities. Chemically incompatible with heparin; therefore, they must not be mixed in the same syringe. However, concomitant anticoagulant therapy may be administered. Incompatible with infusion solutions containing amino acids; therefore, during treatment, vinpocetine infusion must not be used simultaneously with infusion solutions containing amino acids.

Packaging. 2 ml in vials, 5 vials per pack; 5 vials in blister pack per carton.

Prescription category. Prescription only.

Manufacturer.

Limited Liability Company "Research Institute "GNCLS".

LIMITED LIABILITY COMPANY "CORPORATION "ZDOROVTYA".

Manufacturer's address and place of business.

Ukraine, 61057, Kharkiv region, Kharkiv, Vorobiova Street, 8.

(Limited Liability Company "Research Institute "GNCLS")

Ukraine, 61013, Kharkiv region, Kharkiv, Shevchenka Street, 22.

(LIMITED LIABILITY COMPANY "CORPORATION "ZDOROVTYA")