Vinpocetine

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT VINCETIN (VINPOCETINE)

Composition:

Active substance: vinpocetine;

1 tablet contains 5 mg of vinpocetine;

Excipients: lactose monohydrate; corn starch; talc; magnesium stearate.

Pharmaceutical form. Tablets.

Main physicochemical properties: white tablets or white with a slightly grayish tint.

Pharmacotherapeutic group. Psychostimulants and nootropic agents. Vinpocetine.

ATC code N06BX18.

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 blood rheological properties.

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

Vinpocetine stimulates cerebral metabolism: it increases glucose and O2 uptake and utilization by brain tissue. The drug 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. The medicinal product 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 above-mentioned effects, vinpocetine exerts cerebroprotective action.

Vinpocetine improves cerebral microcirculation: it inhibits platelet aggregation, reduces pathologically elevated blood viscosity, increases erythrocyte deformability, and inhibits adenosine uptake, thereby improving O2 transport in tissues by reducing O2 affinity 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); does not cause a "steal effect." Moreover, during administration of the drug, blood supply to damaged (but not yet necrotized) ischemic areas with low perfusion improves (a "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. Radioactivity 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: with repeated oral administration 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 4.83 ± 1.29 hours. Studies using radiolabeled compound showed that vinpocetine is primarily excreted via the kidneys and through the intestine in a ratio of 60:40%. A large 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 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 species studied, the amount of unchanged vinpocetine excreted accounted for 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 the drug's metabolism and absence of accumulation (accumulation).

Changes in pharmacokinetic properties under special conditions (e.g., age, presence of concomitant diseases). Since vinpocetine is primarily indicated for therapy in 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 vinpocetine kinetics in elderly individuals do not significantly differ from those in younger individuals, and furthermore, no accumulation occurs. Standard doses may be used in patients with impaired liver or kidney function, as vinpocetine does not accumulate in such 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.

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

Contraindications.

Pregnancy, breastfeeding period.

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 types of interactions.

Concomitant use of vinpocetine with β-blockers (clonolol, pindolol), cloramide, 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 blood pressure is required 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 cause QT prolongation require periodic ECG monitoring.

Vinpocetine therapy should be initiated only after careful assessment of benefit-risk ratio in patients with increased intracranial pressure, arrhythmia or prolonged QT interval, as well as in those receiving antiarrhythmic agents.

The medicinal product contains lactose. If the patient has known intolerance to certain sugars, medical advice should be sought before taking this medicinal product.

Fertility. Does not affect fertility.

Teratogenic effect. No teratogenic effects have been observed.

Mutagenicity. Vinpocetine has no mutagenic effect.

Carcinogenicity. Vinpocetine has no carcinogenic effect.

Use during pregnancy or breastfeeding.

The use of the drug during pregnancy or 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 maternal blood. No teratogenic or embryotoxic effects of the drug have been observed. However, in preclinical studies with high doses of vinpocetine, placental hemorrhage and spontaneous abortion occurred in some cases, probably due to enhanced placental blood supply.

Breastfeeding: Vinpocetine passes into breast milk. In preclinical studies using a radioactive isotope, radioactivity in breast milk was 10 times higher than in maternal blood. Vinpocetine is contraindicated during breastfeeding due to its passage into breast milk and insufficient clinical safety data in infants. After a single dose of vinpocetine, 0.25% of the administered dose is excreted into breast milk within one hour.

Ability to affect reaction speed when 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.

Take 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 in patients with kidney or liver disease.

Children. The use of the medicinal product in children is contraindicated (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 cardiovascular or other adverse effects.

Adverse Reactions.

Vinpocetine is a safe medication, as confirmed by safety evaluation studies that included data from tens of thousands of patients. The most commonly occurring adverse effects were reported with a frequency of less than 1%. For this reason, the category "common" is absent from the list of adverse reactions.

Adverse reactions are listed below by system organ class, with frequencies according to MedDRA terminology:

• Uncommon: ≥1/1000 to <1/100
• Rare: ≥1/10,000 to <1/1000
• Very rare: <1/10,000

Blood and lymphatic system disorders:
Rare: leucopenia, thrombocytopenia;
Very rare: anemia, erythrocyte agglutination.

Immune system disorders:
Very rare: hypersensitivity.

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

Psychiatric disorders:
Rare: insomnia, sleep disturbance, restlessness, agitation;
Very rare: euphoria, depression.

Nervous system disorders:
Uncommon: headache;
Rare: dizziness, dysgeusia, stupor, hemiparesis, somnolence, amnesia;
Very rare: tremor, seizures.

Eye disorders:
Rare: optic disc edema;
Very rare: conjunctival hyperemia.

Ear and labyrinth disorders:
Uncommon: vertigo;
Rare: hyperacusis, hypoacusis, tinnitus.

Cardiac disorders:
Rare: myocardial ischemia/infarction, angina pectoris, bradycardia, tachycardia, extrasystoles, palpitations;
Very rare: arrhythmia, atrial fibrillation.

Vascular disorders:
Uncommon: arterial hypotension;
Rare: arterial hypertension, flushing, thrombophlebitis;
Very rare: blood pressure fluctuations.

Gastrointestinal disorders:
Uncommon: abdominal discomfort, dry mouth, nausea;
Rare: abdominal pain, constipation, diarrhea, dyspepsia, vomiting;
Very rare: dysphagia, stomatitis.

Skin and subcutaneous tissue disorders:
Rare: erythema, hyperhidrosis, pruritus, urticaria, rash;
Very rare: dermatitis.

General disorders:
Rare: asthenia, weakness, feeling of warmth;
Very rare: chest discomfort, hypothermia.

Investigations (laboratory and instrumental findings):
Uncommon: decreased blood pressure;
Rare: increased blood pressure, increased blood triglycerides, ST segment depression on electrocardiogram, increased/decreased eosinophil count, changes in liver enzyme activity;
Very rare: increased/decreased white blood cell count, decreased red blood cell count, decreased prothrombin time, weight gain.

Shelf life. 4 years.

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

Keep out of reach of children.

Packaging. 10 tablets in a blister pack, 3 blisters per carton.

Prescription status. Prescription only.

Manufacturer.

Limited Liability Company "Research Plant 'GNCLS'" or
Limited Liability Company "FARMEKS GROUP", or
LIMITED LIABILITY COMPANY "CORPORATION 'ZDOROVTYA'".

Manufacturer's location and address of business operations.

Ukraine, 61057, Kharkiv region, city of Kharkiv, Vorobiova Street, building 8.
(Limited Liability Company "Research Plant 'GNCLS')

Ukraine, 08301, Kyiv region, city of Boryspil, Shevchenka Street, building 100.
(Limited Liability Company "FARMEKS GROUP")

Ukraine, 61013, Kharkiv region, city of Kharkiv, Shevchenka Street, building 22.
(LIMITED LIABILITY COMPANY "CORPORATION 'ZDOROVTYA')