Vinpocetine-darnitsa

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT VINCETIN-DARNITSA (Vinpocetin-Darnitsa)

Composition:

Active substance: vinpocetin;

1 ml of the preparation contains 5 mg of vinpocetin;

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

Pharmaceutical form. Concentrate for solution for infusion.

Main physicochemical properties: clear colorless or slightly greenish liquid.

Pharmacotherapeutic group.
Psychostimulants and nootropics. Vinpocetin. ATC code N06BX18.

Pharmacological properties.

Pharmacodynamics.

The active substance of the medicinal product – vinpocetine – exerts beneficial effects on brain metabolism and improves cerebral blood flow, as well as enhances blood rheological properties.

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

Stimulates cerebral metabolism: increases the uptake and utilization of glucose and O2 by brain tissue. Vinpocetine enhances brain resistance to hypoxia; increases transport of glucose – 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 medicinal product increases 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 aforementioned effects, vinpocetine exerts cerebroprotective action.

Improves microcirculation in the brain: 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.

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." Furthermore, during administration of the medicinal product, blood supply to damaged (but not yet necrotized) ischemic areas with low perfusion improves (the so-called "reverse steal effect").

Pharmacokinetics.

After intravenous administration, the drug is bound to plasma proteins by 66%. Maximum concentrations in brain tissue are observed 2–4 hours after administration.

The volume of distribution is 246.7 ± 88.5 L, indicating extensive tissue binding of vinpocetine. During studies, the highest concentrations were found in the liver and gastrointestinal tract.

Metabolized in the liver. The main metabolite of vinpocetine is apovincaminic acid (AVA) – 20–30%, as well as hydroxyvinpocetine, hydroxy-AVA, dihydroxy-AVA-glycinate, and their conjugates with glucuronides and/or sulfates.

Vinpocetine does not accumulate in the body. Impaired liver or kidney function does not affect vinpocetine metabolism.

Excreted from the body via the kidneys (approximately 60%) and the intestine (approximately 40%). The elimination half-life is 4–5 hours.

Changes in pharmacokinetic properties (e.g., due to age or concomitant diseases). Since vinpocetine is indicated primarily for the treatment of elderly patients, in whom changes in drug kinetics are observed (reduced absorption, altered distribution and metabolism, decreased excretion), 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 the kinetics of vinpocetine 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 these patients, allowing prolonged administration.

Clinical characteristics.

Indications.

Neurology: various forms of cerebrovascular pathology (conditions following stroke, vertebro-basilar insufficiency, vascular dementia, cerebral atherosclerosis, post-traumatic and hypertensive encephalopathy). The medicinal product helps reduce psychological and neurological symptoms in cerebrovascular disorders.

Ophthalmology: chronic vascular diseases of the choroid and retina (e.g., thrombosis, obstruction of the central retinal artery or vein).

Otorhinolaryngology: age-related hearing loss in acute vascular pathology, toxic (drug-induced) hearing damage or hearing impairment of other origin (idiopathic, noise-induced), Meniere’s disease, tinnitus.

Contraindications.

Hypersensitivity to the active substance or to other components of the medicinal product; acute phase of hemorrhagic cerebral stroke; severe forms of ischemic heart disease; severe forms of arrhythmia.

Pregnancy, breastfeeding period.

Use of the medicinal product in children is contraindicated (due to lack of data from adequate clinical studies).

Interaction with other medicinal products and other types of interactions.

When vinpocetine is used concomitantly with other medicinal products, the following interactions are possible:

with α-methyldopa – enhanced hypotensive effect; regular monitoring of blood pressure is recommended when these medicinal products are used together;

with heparin – increased risk of bleeding.

In clinical studies, concomitant use of vinpocetine with β-adrenoblockers (chloranolol, pindolol), clomethiazole, glyburide, digoxin, acenocoumarol, hydrochlorothiazide was not associated with any interaction.

Despite the lack of clinical study data, it is recommended to use vinpocetine cautiously with medicinal products affecting the central nervous system, antiarrhythmic agents, antihypertensive agents, anticoagulants, and fibrinolytics.

The medicinal product is incompatible with alcohol.

Special precautions for use

The medicinal product should be used only after careful assessment of benefits and risks in patients with increased intracranial pressure, arrhythmia, or QT interval prolongation syndrome, as well as when used concomitantly with antiarrhythmic agents.

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

The medicinal product should be used with caution in patients with hepatic impairment, poor tolerance to vincamine alkaloids, or when used concomitantly with antihypertensive medicinal products.

The medicinal product is not recommended for use in patients with labile arterial pressure and low vascular tone.

This medicinal product contains a small amount of sorbitol. If you have been diagnosed with intolerance to certain sugars, consult your physician before taking this medicinal product.

Due to the presence of sodium metabisulfite, the medicinal product may rarely cause hypersensitivity reactions and bronchospasm.

Use during pregnancy or breastfeeding.

Pregnancy. The medicinal product crosses the placental barrier, but concentrations detected in the placenta and fetal blood are lower than those in maternal blood. No teratogenic or embryotoxic effects have been observed. In animal studies, administration of high doses of vinpocetine was associated in some cases with placental hemorrhage and miscarriage, primarily due to enhanced placental circulation.

Use of the medicinal product during pregnancy is contraindicated.

Breastfeeding. The medicinal product passes 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 one hour amounts to 0.25% of the administered dose.

Use of the medicinal product during breastfeeding is contraindicated, as vinpocetine passes into maternal milk and there are no data on its effects on the newborn.

Ability to influence reaction speed when driving or operating machinery.

There are no data on the ability of the medicinal product to affect reaction speed when driving or operating machinery; however, the possibility of adverse reactions affecting the nervous system (such as somnolence, dizziness, and vertigo) should be taken into account.

Method of Administration and Dosage.

The medicinal product should be administered intravenously only as a slow drip infusion (infusion rate should not exceed 80 drops per minute).

The medicinal product is contraindicated for subcutaneous, intramuscular, and undiluted intravenous injection.

The medicinal product may be diluted with physiological saline or infusion solutions containing glucose.

The infusion solution should be used within 3 hours after preparation.

The initial daily dose of the medicinal product is usually 20 mg diluted in 500 ml of infusion solution. If necessary, the dose may be increased over 2–3 days up to 1 mg/kg body weight per day, depending on the patient's tolerance of the medicinal product.

The average daily dose of the medicinal product is 50 mg, diluted in 500 ml of infusion solution, calculated for a body weight of 70 kg.

The average duration of treatment course is 10–14 days.

After completion of the infusion therapy course, continuation of treatment with the medicinal product in tablet form is recommended.

Patients with hepatic and renal impairment.

There is no need for dose adjustment of the medicinal product.

Children.

Due to lack of data from appropriate clinical studies, the medicinal product should not be used in children.

Overdose.

Cases of overdose have not been reported. Based on published data, administration of the medicinal product at a dose of 1 mg/kg body weight can be considered safe. Since there are no data regarding the use of the medicinal product at doses exceeding the specified dose, administration of higher doses is not permitted.

Adverse reactions

Adverse reactions were most likely to occur at a frequency of less than 1%. For this reason, the "Frequent" category is absent in the table below.

Undesirable effects are listed below by system organ classes and according to MedDRA terminology regarding frequency of occurrence:

Reporting of suspected adverse reactions.

Reporting of suspected adverse reactions after marketing authorization of a medicinal product is an important procedure. It enables continuous monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals are required to report any suspected adverse reactions through the national reporting system.

Shelf life. 3 years.

Storage conditions.

Store in the original packaging at a temperature not exceeding 25 °C. Do not freeze.

Keep out of reach of children.

Incompatibilities.

Vinpocetine-Darnytsia is pharmaceutically incompatible with heparin; therefore, they must not be administered in the same syringe.

The vinpocetine solution is chemically incompatible with infusion solutions containing amino acids; hence, such solutions must not be used for dilution of the Vinpocetine-Darnytsia concentrate.

Packaging.

2 ml in an ampoule; 5 ampoules in a blist er pack; 2 blister packs in a carton; 10 ampoules in a blister pack; 1 blister pack in a carton.

Prescription status. Prescription only.

Manufacturer. JSC "Pharmaceutical Company "Darnitsya".

Manufacturer's address and location of operations.

13, Boryspylska Street, Kyiv, 02093, Ukraine.