Oxopotin

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT OXOPOTINE® (OXOPOTINE®)

Composition:

Active substance: vinpocetine;

1 tablet contains 5 mg of vinpocetine;

Excipients: lactose monohydrate, hydroxypropylcellulose, magnesium stearate, talc.

Pharmaceutical form. Tablets.

Main physico-chemical properties: white, odorless, flat, round tablets with a diameter of 6 mm; on one side the proprietary logo is imprinted, on the other side — a score line.

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, improves cerebral blood flow, and 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. It enhances the neuroprotective effect of adenosine.

Vinpocetine stimulates cerebral metabolism: it increases the uptake and utilization of glucose and O2 by brain tissue. The drug enhances brain resistance to hypoxia; increases the 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. It elevates ATP concentration and the ATP/AMP ratio (adenosine triphosphate/adenosine monophosphate), enhances noradrenaline and serotonin metabolism in the brain, stimulates the ascending noradrenergic system, and possesses antioxidant activity—overall, these effects result in a cerebroprotective action of vinpocetine.

Vinpocetine improves cerebral microcirculation: the drug inhibits platelet aggregation, reduces pathologically elevated blood viscosity, increases erythrocyte deformability, and inhibits adenosine uptake; it improves O2 transport in tissues by reducing the affinity of O2 to erythrocytes.

Vinp combustive 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); does not cause a "steal effect." Additionally, during drug administration, blood supply improves in damaged (but not yet necrotized) ischemic areas with low perfusion ("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 to rats, radiolabeled vinpocetine was found in 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: protein binding in blood 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 clearance value of vinpocetine in plasma (66.7 L/h) exceeds its hepatic clearance (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. Elimination half-life in humans is 4.83 ± 1.29 hours. Studies using radiolabeled compound showed that elimination occurs mainly via the kidneys and intestine (60% and 40%, respectively). The highest amount of radiolabel in rats and dogs was found in bile, but significant enterohepatic recirculation was not observed. Apovincaminic acid is excreted by the kidneys via simple glomerular filtration; the elimination 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), formed in humans at 25–30%. After oral administration, the area under the plasma concentration-time curve (AUC) of AVA is twice higher than 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 studied species, 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 absence of need for dose adjustment in patients with liver or kidney disease, due to the drug's metabolism and lack of accumulation.

Changes in pharmacokinetic properties under special conditions (e.g., age, concomitant diseases). Since vinpocetine is primarily indicated for treatment of elderly patients, in whom altered pharmacokinetics of drugs (reduced absorption, altered distribution and metabolism, reduced 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 the pharmacokinetics of vinpocetine in elderly patients does not significantly differ from that in younger individuals, and no accumulation occurs.

In patients with impaired liver or kidney function, standard doses of the drug can be used, as vinpocetine does not accumulate in the body of such patients, allowing for 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 sensorineural hearing loss, Ménière’s disease, and tinnitus.

Contraindications.

Hypersensitivity to the active substance or to any of the excipients. Pregnancy, breastfeeding period.

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

It is contraindicated to administer the drug to women of reproductive age who do not use a reliable method of contraception.

Interaction with other medicinal products and other forms of interaction.

Concomitant use of vinpocetine with β-blockers (chloranolol, pindolol), clomipramide, glyburide, 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 arterial pressure is necessary when using this combination of drugs.

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. Interaction with antihypertensive drugs cannot be excluded.

Special precautions for use.

The presence of prolonged QT syndrome and the use of drugs that may cause QT prolongation require periodic ECG monitoring.

If a patient has increased intracranial pressure, arrhythmia or prolonged QT syndrome, or is receiving antiarrhythmic drugs, therapy may be initiated only after careful assessment of the benefit-risk ratio associated with the use of the drug.

This medicinal product contains lactose monohydrate. Patients with rare hereditary conditions such as galactose intolerance, lactase deficiency, or glucose-galactose malabsorption should not take this medicine (1 Oxopotine tablet contains 66.55 mg of lactose).

Use during pregnancy or breastfeeding.

Use of the medicinal product during pregnancy or breastfeeding is contraindicated.

Reproductive studies. According to study results, vinpocetine did not affect fertility in male or female animals. Oral administration of vinpocetine to pregnant animals resulted in developmental toxicity in fetuses, including malformations at clinically relevant exposures expressed as mg/m^2^ of body surface area. In addition, embryofetal mortality was observed in animals treated with high doses.

Pregnancy: Vinpocetine crosses the placental barrier; however, drug concentrations in the placenta and fetal blood are lower than in the pregnant woman's blood. The drug has not shown teratogenic effects. In preclinical studies using high doses of the drug, 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 adult animal blood. The use of vinpocetine during breastfeeding is contraindicated due to transfer of vinpocetine into breast milk and the lack of sufficient clinical safety data in nursing 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 vehicles or operating machinery.

There are no data on the effect of vinpocetine on the ability to drive vehicles or operate machinery; however, caution should be exercised due to the potential occurrence of somnolence, dizziness, and vertigo during treatment with the drug.

Dosage and Administration.

Take orally after meals. The daily dose for adults is 15–30 mg (5–10 mg three times daily). The duration of treatment is determined individually by a physician.

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

Children.

This medicinal product must not be used in children (due to lack of clinical data).

Overdose.

Symptoms of overdose are unknown. A daily dose of 60 mg is considered safe. A single intake of 360 mg of vinpocetine was not associated with the development of any cardiovascular or other adverse effects.

Adverse Reactions.

Oxopotine is a safe medication, 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 were reported at a frequency of less than 1%.

The adverse reactions listed below are categorized by organ systems and frequency of occurrence according to MedDRA terminology [Medical Dictionary for Regulatory Activities].

Blood and lymphatic system disorders: leucopenia, thrombocytopenia (uncommon); anaemia, erythrocyte agglutination (very rare).

Immune system disorders: hypersensitivity (very rare).

Metabolism and nutrition disorders: hypercholesterolaemia (uncommon); decreased appetite, anorexia, diabetes mellitus (uncommon).

Psychiatric disorders: insomnia, sleep disturbance, restlessness, excitement (uncommon); euphoria, depression (very rare).

Nervous system disorders: nervousness, headache (uncommon); dizziness, dysgeusia, stupor, hemiparesis, somnolence, amnesia (uncommon); paraesthesia, tremor, convulsions (very rare).

Eye disorders: optic disc swelling (uncommon); conjunctival hyperaemia (very rare).

Ear and labyrinth disorders: vertigo (uncommon); hyperacusis, hypoacusis, tinnitus (uncommon).

Cardiac disorders: QT interval prolongation, ischaemia/myocardial infarction, angina pectoris, bradycardia, tachycardia, extrasystoles, palpitations (uncommon); arrhythmia, atrial fibrillation (very rare).

Vascular disorders: arterial hypotension (uncommon); arterial hypertension, flushing, thrombophlebitis (uncommon); blood pressure fluctuations (very rare).

Gastrointestinal disorders: abdominal discomfort, dry mouth, nausea (uncommon); epigastric pain, constipation, diarrhoea, dyspepsia, vomiting (uncommon); dysphagia, stomatitis (very rare).

Skin and subcutaneous tissue disorders: erythema, hyperhidrosis, pruritus, urticaria, rash (uncommon); dermatitis (very rare).

General disorders: asthenia, weakness, feeling of warmth (uncommon); chest discomfort, hypothermia (very rare).

Investigations: decreased blood pressure (uncommon); increased blood pressure, increased blood triglycerides, ST segment depression on electrocardiogram, increased/decreased eosinophil count, changes in liver enzyme activity (uncommon); increased/decreased white blood cell count, decreased red blood cell count, decreased prothrombin time, weight gain (very rare).

Reporting of suspected adverse reactions.

Reporting suspected adverse reactions after marketing authorization is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals and patients are encouraged to report any suspected adverse reactions and lack of efficacy via the Automated Pharmacovigilance Information System at: https://aisf.dec.gov.ua.

Shelf life.

5 years.

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

Storage conditions.

Store in a dry, protected from light and inaccessible to children place at a temperature not exceeding 25°C.

Packaging.

25 tablets in a blister, 1 or 2 blisters per cardboard box.

Prescription status.

Prescription only.

Manufacturer.

COVEX S.A.

COVEX S.A.

Manufacturer's address.

Calle Del Acero 25, Poligono Industrial Sur Navarrosillos, Colmenar Viejo, Madrid, 28770, Spain.

Calle Del Acero 25, Poligono Industrial Sur Navarrosillos, Colmenar Viejo, Madrid, 28770, Spain.

Marketing authorization holder.

COVEX S.A.

COVEX S.A.

Address of marketing authorization holder.

C/Acero, 25, Poligono Industrial Sur, 28770 Colmenar Viejo, Madrid, Spain.

C/Acero, 25, Poligono Industrial Sur, 28770 Colmenar Viejo, Madrid, Spain.