Vicefrol

INSTRUCTION FOR MEDICAL USE OF THE MEDICINAL PRODUCT VICEBROL (VICEBROL®)

Composition:

Active substance: vinpocetine;

1 tablet contains vinpocetine 5 mg;

Excipients: lactose monohydrate, microcrystalline cellulose, pregelatinized starch, magnesium stearate.

Pharmaceutical form. Tablets.

Main physicochemical characteristics: white, round, biconvex tablets.

Pharmacotherapeutic group.

Psychoanaleptic 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 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. It inhibits potential-dependent Na+- and Ca2+-channels, as well as NMDA and AMPA receptors. The drug enhances the neuroprotective effect of adenosine.

Vinpocetine stimulates cerebral metabolism: it increases glucose and oxygen uptake and utilization by brain tissue. The drug enhances brain resistance to hypoxia; increases 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. The drug increases adenosine triphosphate (ATP) concentration and the ATP/AMP ratio; enhances metabolism of norepinephrine and serotonin in the brain; stimulates the ascending noradrenergic system; possesses antioxidant activity. As a result of all the above-mentioned effects, vinpocetine exerts cerebroprotective action.

Vinpocetine improves microcirculation in the brain: the drug inhibits platelet aggregation, reduces pathologically increased blood viscosity, enhances erythrocyte deformability, and inhibits adenosine uptake, thereby improving oxygen transport in tissues by reducing oxygen affinity to erythrocytes.

Vinpocetine selectively increases cerebral blood flow: the drug 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, during treatment, 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 gastrointestinal tract. The compound does not undergo metabolism during passage through the intestinal wall.

Distribution. In studies involving oral administration of the drug in 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 blood.

In humans: plasma protein binding 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 (66.7 L/h) in plasma exceeds its hepatic clearance (50 L/h), suggesting extrahepatic metabolism of the compound.

Metabolism. The main metabolite of vinpocetine is apovincaminic acid (AVA), accounting for 25–30%. After oral administration, the area under the concentration-time 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 vinpocetine dose was excreted unchanged.

An important property of vinpocetine is the lack of need for dose adjustment in patients with liver or kidney disease, due to its metabolism and absence of accumulation (cumulation).

Excretion. After repeated oral administration 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 excretion occurs mainly via the kidneys and intestine in a ratio of 60:40%. A large amount of radiolabeled compound was found in the bile of rats and dogs, but significant enterohepatic circulation was not observed. Apovincaminic acid is excreted by the kidneys via simple glomerular filtration; its elimination half-life varies depending on the dose and route of vinpocetine administration.

Changes in pharmacokinetic properties under special conditions (e.g., in specific age groups or in the presence of concomitant diseases). Since vinpocetine is indicated primarily for therapy in 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 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 disease.

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 and breastfeeding period.

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

Interaction with other medicinal products and other forms of interaction.

Concomitant use of vinpocetine with β-blockers (chloranolol, pindolol), clomethiazide, glybenclamide, digoxin, acenocoumarol, or hydrochlorothiazide has not been associated with any interaction in clinical studies.

Concomitant use of vinpocetine and α-methyldopa may sometimes lead to a slight enhancement of the hypotensive effect; therefore, regular monitoring of blood pressure is required when using this combination. Despite the absence of clinical data confirming possible interactions, caution is recommended when co-administering vinpocetine with drugs affecting the central nervous system, as well as in cases of concomitant antiarrhythmic and anticoagulant therapy.

Special precautions for use.

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

In patients with increased intracranial pressure, arrhythmias or prolonged QT interval, as well as during treatment with antiarrhythmic drugs, therapy with this drug should be initiated only after careful assessment of benefits and risks associated with its use.

This medicinal product contains lactose monohydrate. Patients with such rare hereditary conditions as galactose intolerance, Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicinal product.

Use during pregnancy or breastfeeding.

The use of this drug during pregnancy or breastfeeding is contraindicated.

Pregnancy. Vinpocetine crosses the placental barrier; however, the concentration of the drug in the placenta and fetal blood is lower than in the blood of the pregnant woman. Teratogenic effects of the drug have not been observed. In preclinical studies using high doses of the drug, placental bleeding and spontaneous abortion occurred in some cases, likely due to enhanced placental blood supply.

Breastfeeding. Vinpocetine is excreted into breast milk. In studies using a radioactive isotope, radioactivity in breast milk was 10 times higher than in the blood of adult animals. The use of vinpocetine during breastfeeding is contraindicated due to its excretion into breast milk and the lack of sufficient clinical data on safety for nursing infants. Within one hour after a single dose of vinpocetine, 0.25% of the administered dose is excreted into breast milk.

Ability to affect reaction speed when driving or operating machinery.

There are no data on the effect of vinpocetine on the ability to drive 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 a day). The duration of treatment is determined individually by a physician.

Dosage adjustment is not required in patients with kidney or liver disease.

Children.

The drug is not used in children (due to lack of clinical data).

Overdose.

Symptoms of overdose are unknown. According to published data, a dose of 60 mg/day is safe. A single intake of 360 mg of vinpocetine was not accompanied by the development of any cardiovascular or other adverse effects.

Side effects

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

Immune system disorders: hypersensitivity.

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

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

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

Eye disorders: optic disc edema, conjunctival hyperemia.

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

Cardiac disorders: myocardial ischemia/infarction, angina pectoris, bradycardia, tachycardia, extrasystoles, palpitations, arrhythmia, atrial fibrillation, arterial hypotension, arterial hypertension, hot flushes, thrombophlebitis, blood pressure fluctuations.

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

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

General disorders: asthenia, weakness, feeling of warmth, chest discomfort, hypothermia.

Investigations: decreased blood pressure, increased blood pressure, increased blood triglyceride levels, ST segment depression on electrocardiogram, increased/decreased eosinophil count, changes in liver enzyme activity, increased/decreased white blood cell count, decreased red blood cell count, decreased prothrombin time, weight gain.

Shelf life. 3 years.

Storage conditions.

Store at a temperature not exceeding 25 °C. Keep out of reach of children.

Packaging.

10 tablets in a blister; 5 blisters in a cardboard box.

Prescription status. Prescription only.

Manufacturer.

Biofarm Ltd.

Manufacturer's address and place of business:

13 Valbzhiska Street, 60-198 Poznan, Poland.