Cavinton

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT KAVINTON (CAVINTON)

Composition:

Active substance: vinpocetine;

1 tablet contains 5 mg of vinpocetine;

Excipients: colloidal anhydrous silicon dioxide, magnesium stearate, talc, corn starch, lactose monohydrate.

Pharmaceutical form. Tablets.

Main physicochemical characteristics: white or almost white, flat, round tablets with bevelled edges, approximately 9 mm in diameter, odourless, with the engraving "CAVINTON" on one side.

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 favorably affects brain metabolism, improves cerebral blood flow, and enhances blood rheological properties.

Vinpocetine exerts 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. Vinpetocine enhances the neuroprotective effect of adenosine.

Vinpocetine stimulates cerebral metabolism: the drug increases glucose and O₂ uptake and utilization by brain tissue. It enhances brain resistance to hypoxia; increases glucose transport—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 GMP phosphodiesterase (PDE); increases levels of cAMP and cGMP in the brain. The drug elevates ATP concentration and the ATP/AMP ratio; enhances noradrenaline and serotonin metabolism in the brain; stimulates the ascending noradrenergic system; possesses antioxidant activity. As a result of all these effects, vinpocetine exerts a cerebroprotective action.

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

Vinpocetine selectively increases cerebral blood flow: the drug increases the cerebral fraction of cardiac output; reduces cerebral vascular resistance without affecting systemic circulation parameters (arterial pressure, cardiac output, pulse rate, total peripheral resistance); the drug does not cause a "steal effect." Moreover, during treatment, 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 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 administration. Radioactive tracer concentration 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. Vinpocetine clearance in plasma (66.7 L/h) exceeds 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 showed that the primary elimination routes are renal and intestinal, in a ratio of 60%:40%. The highest amount of radiolabeled compound in rats and dogs was found in bile, but significant enterohepatic circulation was not observed. Apovincaminic acid is excreted by the kidneys via simple glomerular filtration; the 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 all 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 the drug's metabolism and absence of accumulation.

Changes in pharmacokinetic properties under special conditions (e.g., age, concomitant diseases). Since vinpocetine is indicated for use primarily in elderly patients, in whom changes in drug kinetics—such as reduced absorption, altered distribution and metabolism, and decreased elimination—are commonly observed, studies evaluating the drug's kinetics in this age group, especially with long-term use, were necessary. Results of such studies demonstrated that vinpocetine kinetics in elderly patients 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 these patients, allowing for prolonged treatment.

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 associated with cerebrovascular pathology.

Ophthalmology. For the treatment of chronic vascular pathology of the choroid and retina.

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

Contraindications.

Pregnancy, breastfeeding. Contraindicated in women of reproductive age who do not use a reliable method of contraception.

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

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

Interaction with other medicinal products and other forms of interaction.

During clinical studies, no interactions were observed when vinpocetine was administered concomitantly with beta-blockers such as chloranolol and pindolol, or with clomipramide, glybenclamide, digoxin, acenocoumarol, or hydrochlorothiazide. In isolated cases, some additional effect was observed when alpha-methyldopa and vinpocetine were used concomitantly; therefore, regular monitoring of blood pressure is necessary when this combination of drugs is used.

Although clinical data have not confirmed interactions, caution is recommended when vinpocetine is used concomitantly with medicinal products affecting the central nervous system, as well as during concomitant antiarrhythmic and anticoagulant therapy.

Special precautions for use

In cases of increased intracranial pressure, when administering antiarrhythmic agents, or in the presence of arrhythmias and long QT interval syndrome, the drug should be used only after careful assessment of the benefit-risk ratio of therapy.

Prolongation of the QT interval

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

Excipients

In patients with lactose intolerance, it should be noted that the medicinal product contains lactose: one tablet of Cavinton contains 140 mg of lactose. This medicinal product should not be administered to patients with rare hereditary disorders of galactose intolerance, complete lactase deficiency, or glucose-galactose malabsorption.

Fertility. Does not affect fertility.

Mutagenicity. Vinpocetine has no mutagenic effect.

Carcinogenicity. Vinpocetine has no carcinogenic effect.

Use during pregnancy or breastfeeding.

Vinpocetine is contraindicated during pregnancy, breastfeeding, and in women of childbearing potential who are not using a reliable method of contraception.

Fertility studies. According to study results, vinpocetine did not affect fertility in male or female animals. Oral administration of vinpocetine to animals during pregnancy resulted in developmental toxicity, including developmental malformations, at clinically relevant exposures based on mg/m² body surface area. In addition, embryofetal lethality was observed in animals at high doses.

Pregnancy. Vinpocetine crosses the placenta but is found in lower concentrations in placental tissue and fetal blood than in maternal blood. Reproductive toxicity, including developmental malformations, has been observed in animal studies. In animal studies, administration of high doses of vinpocetine was associated in some cases with placental hemorrhage and abortion, primarily due to increased placental blood flow.

Breastfeeding. Vinpocetine is excreted into breast milk. In studies using radiolabeled vinpocetine, radioactivity in breast milk was 10 times higher than in maternal blood. The amount excreted into breast milk within 1 hour amounts to 0.25% of the administered dose. Since vinpocetine passes 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 when driving vehicles or operating machinery.

Studies investigating the effect on the ability to drive vehicles or operate machinery have not been conducted. However, the possibility of somnolence, dizziness, and vertigo occurring during treatment should be taken into account.

Dosage and Administration.

For oral use. The usual dosage is 5–10 mg three times daily (15–30 mg daily). Tablets should be taken after meals.

The duration of treatment is determined individually by a physician.

Renal or hepatic impairment

Patients with kidney or liver disease do not require special dose adjustment.

Children

Cavinton is contraindicated in children.

Overdose

Long-term administration of vinpocetine at a daily dose of 60 mg is also safe. Even a single oral intake of 360 mg of vinpocetine did not cause any clinically significant adverse effects on the cardiovascular system or other effects.

Adverse reactions.

Cavinton is a safe medication, as confirmed by safety assessment studies that included data from tens of thousands of patients and demonstrated that even the most frequently occurring adverse effects did not fall into the category "Common > 1/100" according to MedDRA definitions. In other words, adverse effects with the highest probability of occurrence were recorded at a frequency of less than 1%. For this reason, the category "Common" is absent in the table below.

Undesirable reactions listed below are classified by system organ classes and include frequency of occurrence according to MedDRA terminology:

Shelf life. 5 years.

Storage conditions.

Store at a temperature not exceeding 30 °C in the original packaging to protect from light exposure.

Keep this medication out of the reach of children!

Packaging. 25 tablets in a blister; 2 blisters per cardboard package.

Prescription status. Prescription only.

Manufacturer: Gedeon Richter Plc.

Manufacturer's name and address of the place of business:

H-1103 Budapest, 19-21 Demréti Street, Hungary.