VINPOCETINE-DARNITSA

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT VINOPOCETINE-DARNITSA (VINPOCETINE-DARNITSA)

Composition:

Active substance: vinpocetine;

1 tablet contains 5 mg of vinpocetine;

Excipients: lactose monohydrate, potato starch, magnesium stearate.

Pharmaceutical form. Tablets.

Main physicochemical properties: white-colored, flat cylindrical tablets with a bevel.

Pharmacotherapeutic group. Psychostimulants and nootropic agents. Vinpocetine.

ATC code N06BX18.

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. 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: 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 transport 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 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 with the drug, blood supply improves in damaged (but not yet necrotized) ischemic areas with low perfusion ("reverse steal effect").

Pharmacokinetics

Absorption: rapidly absorbed, and one hour after oral administration, its concentration in the blood reaches maximum levels. Absorption occurs primarily in the proximal segments of the gastrointestinal tract. The drug does not undergo metabolism during passage through the intestinal wall.

Distribution: studies using radiolabeled vinpocetine have shown that after oral administration, the highest radioactivity is found in the liver and gastrointestinal tract. Maximum tissue concentrations are observed 2–4 hours after oral administration. The concentration of vinpocetine in brain tissue does not exceed its concentration in blood. In humans, 66% of vinpocetine is protein-bound; bioavailability after oral administration is 7%; volume of distribution is 246.7 ± 88.5 L, indicating good tissue distribution. The plasma clearance value of vinpocetine (66.7 L/h) exceeds its hepatic clearance (50 L/h), indicating extrahepatic metabolism of the compound.

Metabolism: the main metabolite of vinpocetine, apovincaminic acid (AVA), is formed in humans in amounts of 25–30% during the first pass through the liver. Compared to intravenous administration, the area under the concentration-time curve (AUC) of AVA is doubled after oral administration. Other metabolites of vinpocetine include: hydroxyvinpocetine, hydroxy-AVA, glycinate of dihydroxyapovincaminic acid, and their sulfate and glucuronide conjugates. Liver and kidney diseases do not affect vinpocetine metabolism.

Elimination: with repeated oral administration of the drug at doses of 5 and 10 mg, the pharmacokinetics are linear; plasma concentrations at steady state 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. The drug is excreted in urine and feces in a ratio of 3:2. AVA elimination occurs via glomerular filtration. Elimination half-life depends on the dose of vinpocetine and the dosing regimen.

Elderly patients. Clinical studies have shown no significant differences in the drug's pharmacokinetics between elderly and younger patients; the drug does not accumulate. The drug can be administered at the usual dose to patients with liver and/or kidney disease. The absence of accumulation allows for prolonged treatment courses.

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, Ménière’s disease, and tinnitus.

Contraindications.

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

Interaction with other medicinal products and other forms of interaction.

Concomitant administration of vinpocetine with β-blockers (cloranolol, pindolol), as well as with clopamide, glibenclamide, 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 these drugs are used together.

Despite the lack of clinical data confirming potential interactions, caution is recommended when prescribing vinpocetine concomitantly with medicinal products acting on the central nervous system, antiarrhythmics, and anticoagulants.

Concomitant use of the medicinal product Vinpocetine-Darnytsia and heparin increases the risk of hemorrhagic complications.

Special precautions for use.

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

In patients with increased intracranial pressure, arrhythmia or QT interval prolongation syndrome, as well as in those receiving antiarrhythmic drugs, therapy with this medicinal product should be initiated only after careful assessment of the benefit-risk ratio.

Patients with rare hereditary galactose intolerance, Lapp lactase deficiency, or glucose-galactose malabsorption should not take this medicinal product.

Fertility. No effect on fertility has been observed.

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 this medicinal product during pregnancy or breastfeeding is contraindicated.

Ability to influence reaction rate when driving or operating machinery.

Studies on the influence of this medicinal product on the ability to drive or operate machinery have not been conducted. However, caution should be exercised due to the potential occurrence of somnolence, dizziness, and vertigo during treatment.

Method of administration and dosage.

Administer orally after meals.

Vinpocetine-Darnitsya is recommended for adults at a dose of 5–10 mg (1–2 tablets) three times daily (15–30 mg per day).

Patients with renal or hepatic impairment do not require special dose adjustment.

The duration of treatment is determined individually by the physician.

Children.

The medicinal product is not intended for use in children (due to lack of clinical data).

Overdose.

Cases of overdose have not been reported. 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.

Eye disorders: optic disc edema, conjunctival hyperemia.

Ear and labyrinth disorders: vertigo, hyperacusis, hypoacusis, tinnitus.

Gastrointestinal disorders: abdominal discomfort, dry mouth, nausea, abdominal pain, constipation, diarrhea, dyspepsia, vomiting, dysphagia, stomatitis.

Metabolism and nutrition disorders: hypercholesterolemia, decreased appetite, anorexia, diabetes mellitus, weight increased.

Nervous system disorders: headache, dizziness, dysgeusia, stupor, hemiparesis, somnolence, amnesia, tremor, seizures.

Psychiatric disorders: insomnia, sleep disorders, agitation, restlessness, euphoria, depression.

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

Vascular disorders: hypotension, hypertension, flushing, thrombophlebitis, blood pressure fluctuations.

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

Immune system disorders: hypersensitivity reactions, including rash, pruritus, urticaria.

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

General disorders: asthenia, weakness, hot flushes, chest discomfort, hypothermia.

Investigations: decreased blood pressure, increased blood pressure, increased blood triglycerides, ST segment depression on electrocardiogram, increased/decreased eosinophil count, changes in liver enzyme activity, increased/decreased white blood cell count, decreased erythrocyte count, decreased prothrombin time.

Shelf life. 3 years.

Storage conditions.

Store in a tightly closed container, protected from light and moisture, 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 or 5 blisters per carton.

Prescription status. Prescription only.

Manufacturer. JSC "Pharmaceutical Company "Darnytsia".

Manufacturer's address.

13, Borispilska Street, Kyiv, 02093, Ukraine.