Cavinton forte

INSTRUCTION FOR MEDICAL USE OF THE MEDICINAL PRODUCT KAVINTON FORTE (CAVINTON FORTE)

Composition:

active substance: vinpocetine;

1 tablet contains 10 mg of vinpocetine;

excipients: magnesium stearate; colloidal anhydrous silicon dioxide; talc; lactose monohydrate; maize starch.

Pharmaceutical form. Tablets.

Main physicochemical properties: white or almost white, flat, disc-shaped tablets with a bevel, approximately 8.0 mm in diameter, marked with "10 mg" on one side and a line on the other.

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 and improves cerebral blood flow, as well as enhances blood rheological properties.

Vinpocetine exhibits neuroprotective effects: the drug reduces the harmful effects of cytotoxic reactions caused by excitatory amino acids. It inhibits potential-dependent Na+- and Ca2+-channels, as well as NMDA and AMPA receptors. The drug 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 increases 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 the aforementioned 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 O2 delivery to 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, 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. The value of vinpocetine clearance in plasma (66.7 L/h) exceeds its hepatic clearance (50 L/h), indicating extrahepatic metabolism of the compound.

Elimination. After 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 main elimination routes are via kidneys and intestine in a ratio of 60:40%. The highest amount of radiolabel was found 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 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 25–30%. After oral administration, the area under the plasma 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 all studied species, only a few percent of the administered dose of vinpocetine 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 indicated for treatment primarily in elderly patients, in whom changes in drug kinetics—such as reduced absorption, altered distribution and metabolism, and decreased elimination—are 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 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 prolonged treatment.

Clinical characteristics.

Indications.

Neurology. For the treatment of various forms of cerebrovascular pathology: conditions following cerebrovascular accident (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 uveal tract and retina.
Otorhinolaryngology. For the treatment of age-related sensorineural hearing loss, Ménière's disease, and tinnitus.

Contraindications.

Pregnancy, lactation, and use 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.

Use of the medicinal product in children is contraindicated (due to 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, as well as with clomipramide, glyburide, digoxin, acenocoumarol, or hydrochlorothiazide. In isolated cases, a slight additive effect was observed when alpha-methyldopa and vinpocetine were used concomitantly; therefore, regular monitoring of blood pressure is necessary when this combination 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.

Cavinton may be prescribed after careful assessment of the benefit-risk ratio in patients with increased intracranial pressure, when antiarrhythmic agents are administered, and in patients with arrhythmias or QT interval prolongation syndrome.

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

In patients with lactose intolerance, it should be noted that the drug contains lactose: each tablet of Cavinton Forte (10 mg) contains 83 mg of lactose.

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 reproductive potential who are not using reliable contraception.

Reproductive studies. According to study results, vinpocetine had no effect on fertility in male and female animals. Oral administration of vinpocetine to animals during pregnancy resulted in developmental toxicity, including teratogenic effects at clinically relevant exposures based on mg/m² body surface area. In addition, embryofetal mortality was observed in animals treated with high doses.

Pregnancy. Vinpocetine crosses the placental barrier, but concentrations in placental tissue and fetal blood are lower than in maternal blood. Reproductive toxicity, including developmental abnormalities, 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 in breast milk. In studies using radiolabeled vinpocetine, radioactivity in breast milk was 10 times higher than in maternal blood. The amount excreted in breast milk over one hour amounts to 0.25% of the administered dose. Since vinpocetine is excreted in breast milk and there are no data on its effects on newborns, the use of vinpocetine during breastfeeding is contraindicated.

Ability to influence reaction speed when driving or operating machinery.

No studies have been conducted to evaluate the effect of Cavinton on the ability to drive or operate machinery. However, the potential for somnolence, dizziness, and vertigo during treatment should be considered.

Dosage and Administration.

The usual dosage of the drug is 5–10 mg three times daily (15–30 mg per day). Tablets should be taken after meals.

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

The duration of treatment is determined individually by the physician.

Children.

Cavinton Forte 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 Forte is a safe medication, as confirmed by safety evaluation studies involving data from tens of thousands of patients, demonstrating that even the most frequently occurring adverse effects did not fall into the "common (> 1/100)" category 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 "common" category is absent in the table below.

Adverse reactions listed below are categorized by system organ classes and include the 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.

Keep the medicine out of the reach of children!

Packaging. 15 tablets in a blister. 2 or 6 blisters in a cardboard pack.

Prescription status. Prescription only.

Manufacturer: JSC "Gedeon Richter".

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

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