Vinpocetine - instructions for use, dose, side effects, contraindications

The mechanism of action of vinpocetine consists of several elements: it improves cerebral blood flow and metabolism, has a beneficial effect on the rheological properties of the blood.

The neuroprotective effect is realized by reducing the unfavorable cytotoxic effect of excitatory amino acids. Blocks Na+ - and Ca2 + -channels and NMDA- and AMPA receptors. Selectively inhibits Ca2 + -calmodulin-dependent-cGMP-phosphodiesterase. Increases the exchange of serotonin and norepinephrine in the brain, stimulates the noradrenergic neurotransmitter system and has an antioxidant effect.

Improves microcirculation in the brain due to inhibition of platelet aggregation, a decrease in pathologically increased blood viscosity, increased erythrocyte deformability and inhibition of adenosine reuptake; promotes the transition of oxygen into cells by reducing the affinity of erythrocytes for it.

Selectively increases cerebral blood flow by reducing cerebral vascular resistance without significantly affecting systemic blood circulation parameters (blood pressure (BP), cardiac output, heart rate, total peripheral vascular resistance); does not cause the effect of "stealing".

Pharmacokinetics:

The therapeutic concentration in plasma is 10-20 mt / ml.For parenteral administration, the volume of distribution is 5.3 l / kg. The connection with proteins is 66%, the ground clearance is 66.7 l / h. The half-life is 4.74-5 hours. Easily penetrates through the histohematological barriers (including the blood-brain barrier). Penetrates into breast milk (0.25% within the first hour), through the placental barrier. It is transformed in the liver with the formation of metabolites: apovincamine acid, hydroxidevinpocetine, hydroxyapovic acid, dihydro-vinpocetine-glycinate.

It is excreted by the kidneys and through the gastrointestinal tract in a ratio of 3: 2.

Suction and distribution

In studies with oral administration of the drug in rats, the radiolabeled vinpocetine the highest concentration was found in the liver and in the gastrointestinal tract. The maximum concentration (C_max) in the tissues could be detected after 2-4 h after the application of the drug. The concentration of the radioactive label in the brain did not exceed the concentration in the blood.

The therapeutic concentration in plasma is 10-20 mg / ml. For parenteral administration, the volume of distribution is 5.3 l / kg. In humans, binding to blood proteins is 66%. V_dis 246.7 ± 88.5 l, which means a pronounced binding of the substance in the tissues.Value of clearance vinpocetine (66.7 l / h) exceeds the value in the plasma and in the liver (50 l / h), indicating that the compound of extrahepatic metabolism. Easily penetrates through gistogematicheskie barriers (including the blood-brain barrier). Do not cumulate.

Metabolism

The main metabolite of vinpocetine is apovincamine acid (AVK), which in humans is formed in 25-30%. After oral administration AUC AVK is 2 times higher than that after IV injection, which indicates the formation of AVK in the process of presystemic metabolism of vinpocetine. In other metabolites identified are gidroksivinpotsetin, hydroxy-AVC, AVC-dihydroxy-glycinate and their conjugates with glucuronides and / or sulphates. In any of the studied species, the amount of vinpocetine that was released unchanged was only a few percent of the dose taken.

Excretion

In studies using radiolabelled vinpocetine, it was found that the drug is derived mainly through the kidneys and gastrointestinal tract in a ratio of 60%: 40%. A greater amount of radioactive label in rats and dogs was found in bile, but no significant enterohepatic circulation was noted.Apovincaminic acid is excreted by the kidneys through glomerular filtration, T_1/2this substance varies depending on the dose and method of application of vinpocetine.

Pharmacokinetics in special clinical cases

Due to the peculiarities of vinpocetin metabolism and the absence of cumulation, patients with impaired liver or kidney function do not need a specific dose selection and can be used for a long time.

According to clinical studies, pharmacokinetics of vinpocetine, incl. with prolonged use, in older people does not differ significantly from the pharmacokinetics in young people. Cumulation in the elderly is also absent.

Indications:

- symptomatic therapy of the consequences of ischemic stroke, vascular vertebrobasilar insufficiency, vascular dementia, atherosclerosis of cerebral vessels, posttraumatic, hypertensive encephalopathy;

- chronic vascular diseases of the retina and choroid of the eye;

- perceptual hearing loss, Meniere's disease, tinnitus.

Contraindications:

- acute phase of hemorrhagic stroke, severe ischemic heart disease, severe arrhythmias, hypersensitivity to any of the components of the drug;

- pregnancy (possibly placental bleeding and spontaneous abortion, probably as a result of increased placental blood supply);

- the period of breastfeeding (when using the drug, you must stop breastfeeding);

- age under 18 years (due to insufficient data);

- deficiency of 1,6-diphosphatase fructose.

Carefully:

Be wary appoint patients who take antihypertensive drugs or drugs that increase the interval QT, and also to patients with poor tolerance of alkaloids of the Barvinka small (Vinca minor) and suffering from liver failure.

Pregnancy and lactation:

Contraindicated in pregnancy.

For the duration of treatment, breastfeeding should be discontinued.

Vinpocetin penetrates the placenta, but the plasma concentration in the placenta and in the fetus is lower than that of the mother. Teratogenic and embryotoxic effects were not detected. In studies on animals with the introduction of high doses, placental bleeding and spontaneous abortion arose (presumably as a result of an increase in placental blood flow). Vinpocetine penetrates into breast milk.According to preclinical studies with radioactively labeled vinpocetine, its concentration in the breast milk of animals exceeded that in the mother's blood 10 times. For 1 hour in the milk penetrates 0.25% of the dose.

Dosing and Administration:

The drug is intended only for intravenous drip infusion, administered slowly (infusion rate should not exceed 80 drops / min).

Intravenous administration of undiluted preparation is not allowed. Infusion solution should be administered within 3 hours from the time of preparation!

For the preparation of infusion, you can use a solution of sodium chloride 0.9% or solutions containing dextrose.

The initial daily dose of 20 mg in 500 ml of the infusion solution. Depending on the tolerability, within 2-3 days the dose can be increased to no more than 1 mg / kg / day.

The average duration of treatment is 10-14 days.

The average daily dose at a body weight of 70 kg is 50 mg.

With liver or kidney disease, dose adjustment is not required.

After completing the course of parenteral administration, they switch to oral administration of the drug (10 mg 3 times a day). Before drug cancellation the dose should be gradually reduced.

Side effects:

From the cardiovascular system: ECG change (segment depression ST, lengthening the interval QT, lengthening the interval PR), extrasystole, bradycardia, palpitations, tachycardia - rarely, atrial fibrillation, chest discomfort, changes in blood pressure (more often decrease), ischemia / myocardial infarction, angina pectoris, heart failure, skin redness, thrombosis, phlebitis-sometimes.

From the side of the blood and lymphatic system: thrombocytopenia, agglutination of erythrocytes, anemia.

From the central nervous system: asthenia, sleep disturbances (insomnia or increased drowsiness), dizziness, headache, euphoria, anxiety, depression, unilateral paresis, tremor, loss of consciousness, pre-stupor.

From the side of the organ of vision: hyphema, hypermetropia, visual impairment, myopia, conjunctival hyperemia, edema of the nipple of the optic nerve, diplopia.

From the side of the hearing organ and labyrinthine disorders: hearing loss, hyperacusis, hypoacusia, vertigo, tinnitus.

On the part of the digestive system: anorexia, dry mouth, nausea, hypersalivation, vomiting, heartburn - sometimes.

Allergic reactions: skin rash, hives - rarely, hypersensitivity.

From the side of metabolism: diabetes.

Laboratory data: hypercholesterolemia, increased urea concentration in the blood, increased lactate dehydrogenase activity.

Other: hot flushes, increased sweating - sometimes.

Violations at the place of administration: inflammation at the injection site.

Overdose:

Currently, data on the overdose of vinpocetine are limited.

When an overdose is possible: arterial hypotension, inhibition, nausea, vomiting. Treatment: symptomatic therapy.

Interaction:

Interactions are not observed with simultaneous use with β-blockers (chloranolol, pindolol), clopamid, glibenclamide, digoxin, acenocoumarol and hydrochlorothiazide, imipramine.

The simultaneous use of vinpocetine and α-methyldopa sometimes caused some strengthening of the hypotensive effect, so this treatment requires regular monitoring of blood pressure.

Despite the lack of data confirming the possibility of interaction, it is recommended to exercise caution while using central, antiarrhythmic and anticoagulant drugs with the drugs.

Vinpocetine and heparin are chemically incompatible, so they are not allowed to be administered in the same infusion mixture, however, anticoagulants and vinpocetine can be treated concurrently.

Vinpocetine is incompatible with infusion solutions containing amino acids, so they can not be used to dilute it.

Special instructions:

Presence of the syndrome of the prolonged interval QT and taking medications that elongate the interval QT, requires periodic ECG monitoring.

The preparation contains sorbitol, therefore in patients with diabetes it is necessary to periodically monitor the concentration of glucose in the blood.

In case of fructose intolerance or a deficiency of fructose 1,6-diphosphatase, vinpocetine should be avoided.

Effect on the ability to drive transp. cf. and fur:

Studies on the impact on the ability to drive vehicles were not conducted. When there are undesirable reactions from the nervous system, care should be taken when driving vehicles and working with mechanisms.

Form release / dosage:Concentrate for the preparation of solution for infusions 5 mg / ml.

Packaging:

2 ml into the ampoules of the light-protective glass.

5 ampoules are placed in a contour mesh package made of a polyvinyl chloride film.

1, 2 contour mesh packages are placed in packs of cardboard.

10 ampoules are placed in boxes of cardboard with corrugated paper partitions.

In each pack, the box is enclosed with instructions for use, a scarifier or ampoule knife (when packaging ampoules with a break ring, a point and an incision, the ampoule knife or scarifier does not invest).

Storage conditions:

In the dark place at a temperature of no higher than 25 ° C.

Keep out of the reach of children.

Shelf life:

2 years. Do not use after the expiration date.

Terms of leave from pharmacies:On prescription

Registration number:LP-002430

Date of registration:11.04.2014

Expiration Date:11.04.2019

The owner of the registration certificate:BIOSINTEZ, PAO BIOSINTEZ, PAO Russia

Manufacturer: & nbsp

BIOSINTEZ, PAO Russia

Information update date: & nbsp17.02.2017

Illustrated instructions

Instructions

Vinpocetine (Vinpocetine)