Vinpocetine-pharmak

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

Composition:

Active substance: vinpocetine;

1 ml of concentrate for infusion solution contains 5 mg of vinpocetine, calculated as 100 % substance;

Excipients: glycine, betaine hydrochloride, disodium edetate, propylene glycol, water for injections.

Pharmaceutical form. Concentrate for solution for infusion.

Main physicochemical characteristics: clear colorless or slightly greenish liquid.

Pharmacotherapeutic group.

Psychostimulants. Psychostimulants and nootropic agents. ATC code N06BX18.

Pharmacological Properties

Pharmacodynamics

Vinpocetine is a compound with a complex mechanism of action that exerts beneficial effects on brain metabolism, improves cerebral blood flow, and enhances the rheological properties of blood.

Vinpocetine exhibits neuroprotective effects: it reduces the harmful impact 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 the uptake and utilization of glucose and O₂ by brain tissue. It enhances the brain's resistance to hypoxia; increases the 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); and increases levels of cAMP and cGMP in the brain. The drug elevates ATP concentration and the ATP/AMP ratio; enhances the reuptake of norepinephrine and serotonin in the brain; stimulates the ascending noradrenergic system; possesses antioxidant activity. As a result of these combined effects, vinpocetine exerts a cerebroprotective action.

Vinpocetine improves cerebral microcirculation: it inhibits platelet aggregation, reduces pathologically elevated blood viscosity, increases erythrocyte deformability, and inhibits adenosine uptake. It enhances oxygen transport in tissues by reducing the affinity of oxygen to erythrocytes.

Vinpocetine selectively increases cerebral blood flow: it 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, under the influence of vinpocetine, blood flow improves in damaged (but not yet necrotized) ischemic areas with low perfusion ("reverse steal effect").

Pharmacokinetics

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. The concentration of radioactivity in the brain did not exceed that in the blood.

In humans: plasma protein binding is 66%. Absolute oral bioavailability of vinpocetine is 7%. The volume of distribution is 246.7 ± 88.5 L, indicating extensive tissue binding. The clearance value of vinpocetine (66.7 L/h) exceeds hepatic plasma flow (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 83 ± 1.29 hours. Studies using radiolabeled compound have shown that the primary route of elimination is via urine and feces in a ratio of 60%:40%. A greater amount of radiolabel was found in the bile of rats and dogs, but significant enterohepatic recirculation 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 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 glucuronide and/or sulfate conjugates. In each studied species, only a few percent of the administered 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 primarily indicated for the treatment of elderly patients, in whom changes in drug kinetics—such as reduced absorption, altered distribution and metabolism, and decreased elimination—may occur, 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 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. 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 choroid (vascular layer of the eye) and retina.

Otorhinolaryngology. For the treatment of age-related hearing loss due to acute vascular pathology, toxic (drug-induced) damage, or other types of damage (idiopathic, noise-induced), Ménière’s disease, and tinnitus.

Contraindications.

Acute phase of hemorrhagic cerebral stroke, severe ischemic heart disease, severe forms of arrhythmia.

Pregnancy, lactation period.

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

Pediatric age (due to lack of data from appropriate clinical studies).

Interaction with other medicinal products and other types of interactions.

During clinical studies, no interactions were observed when vinpocetine was used concomitantly with beta-blockers such as clonolol and pindolol, or with clopamide, glyburide, digoxin, acenocoumarol, or hydrochlorothiazide. In isolated cases, a slight additive effect was observed when alpha-methyldopa was used concomitantly with vinpocetine; therefore, regular monitoring of arterial pressure is required 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.

In patients with increased intracranial pressure, arrhythmia or QT interval prolongation syndrome, as well as when using antiarrhythmic drugs, vinpocetine therapy should be initiated only after careful assessment of benefits versus risks associated with the drug use.

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

Precautionary measures: Vinpocetine is not recommended in patients with labile arterial pressure and low vascular tone.

Use with caution in patients receiving antihypertensive agents, as well as in patients with poor tolerance to alkaloids of Vinca minor and in patients with hepatic insufficiency.

Use during pregnancy or breastfeeding.

Vinpocetine is contraindicated during pregnancy and breastfeeding.

Pregnancy. Vinpocetine crosses the placental barrier, but concentrations in fetal blood and placental tissue are lower than 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 abortion, predominantly due to enhanced placental circulation.

Breastfeeding. Vinpocetine is excreted into breast milk. In studies using radiolabeled vinpocetine, radioactivity in breast milk was ten times higher than in maternal blood. The amount excreted into milk within 1 hour amounts to 0.25% of the administered dose. Since vinpocetine passes into breast milk and there are no data on its effects on newborns, the use of vinpocetine during breastfeeding is contraindicated.

Ability to influence reaction rate while driving or operating machinery.

There are no data on the effect of vinpocetine on the ability to drive or operate machinery; however, the possibility of somnolence, dizziness, and vertigo occurring during treatment should be taken into account.

Method of Administration and Dosage.

Only as a slow intravenous drip infusion! (The infusion rate must not exceed a maximum of 80 drops/minute!)

The drug must not be administered intramuscularly; also, the drug must not be administered intravenously without prior dilution!

The usual initial daily dose for adults is 20 mg in 500 ml of infusion solution. This dose may be increased up to 1 mg/kg body weight per day over 2–3 days, depending on patient tolerance.

The average duration of treatment course is 10–14 days; the usual daily dose is 50 mg/day (50 mg in 500 ml of infusion solution), calculated for a body weight of 70 kg.

After completion of the intravenous infusion course, it is recommended to continue treatment with vinpocetine tablets.

Vinpocetine-Farmak, concentrate for infusion solution, can be diluted with physiological saline or infusion solutions containing glucose (e.g., Salsole, Ringer, Rindex, Reomacrodex). The infusion solution should be used within 3 hours after preparation.

Dosage adjustment is not required in patients with renal or hepatic impairment.

Children.

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

Overdose.

No cases of overdose have been reported. According to literature data, administration of the drug at a dose of 1 mg/kg body weight may be considered safe. Since there is no available information on the use of doses exceeding this amount, administration of higher doses is not permitted.

Adverse reactions.

Vinpocetine is a safe drug, as confirmed by safety evaluation studies that included data from tens of thousands of patients and demonstrated that even the most frequently occurring adverse effects did not fall under 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 "Common" frequency category is absent in the table below.

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

Table 1.

Shelf life. 3 years.

Do not use the medicinal product after the expiry date stated on the packaging.

Storage conditions.

Store in the original packaging at a temperature not exceeding 25 °C. Keep out of reach of children.

Incompatibility. The concentrate for infusion solution is chemically incompatible with heparin; therefore, they must not be mixed in the same syringe. However, concomitant anticoagulant therapy may be administered.

The concentrate for infusion solution is also incompatible with infusion solutions containing amino acids; therefore, during vinpocetine infusion therapy, it should not be used simultaneously with infusion solutions containing amino acids.

Packaging. 2 ml in an ampoule. 10 ampoules per pack.

Prescription status. Prescription only.

Manufacturer. JSC "Pharmak".

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

74, Kyrylivska Street, Kyiv, 04080, Ukraine.