Vazoserk duo

INSTRUCTION FOR MEDICAL USE OF THE MEDICINAL PRODUCT VASOSERCDUO (VASOSERCDUO)

Composition:

Active substance: betahistine;

One tablet contains 24 mg of betahistine dihydrochloride;

Excipients: mannite (E 421), microcrystalline cellulose, polypaldon XL, citric acid monohydrate, talc, colloidal anhydrous silicon dioxide, stearic acid.

Pharmaceutical form. Tablets.

Main physicochemical properties: white, round tablets with a break line on one side.

Pharmacotherapeutic group. Agents for the treatment of vestibular disorders.

ATC code N07CA01.

Pharmacological properties.

Pharmacodynamics.

The mechanism of action of betahistine has been only partially elucidated. Available data come from studies conducted in animals and in humans.

Effect of betahistine on the histaminergic system

Betahistine has been shown to act as a partial agonist at H1 receptors and as an antagonist at H3 receptors of histamine in nervous tissue, with minimal activity at H2 histamine receptors. Betahistine increases histamine turnover and release by blocking presynaptic H3 receptors and inducing a down-regulation process of these H3 receptors.

Betahistine may increase blood flow to the cochlear region as well as to the entire brain Pharmacological studies in animals have demonstrated improved circulation in the vessels of the stria vascularis of the inner ear, possibly due to relaxation of precapillary sphincters in the microcirculatory system of the inner ear. Betahistine has also been shown to increase cerebral blood flow in humans.

Betahistine promotes vestibular compensation

Betahistine accelerates recovery of vestibular function after unilateral neurectomy in animals, thereby speeding up and facilitating the process of central vestibular compensation. This effect is characterized by enhanced regulation of histamine turnover and release, mediated by H3 receptor antagonism. In humans, treatment with betahistine also reduced the recovery time of vestibular function following neurectomy.

Betahistine alters neuronal activity in the vestibular nuclei

It has also been established that betahistine exerts a dose-dependent inhibitory effect on spike potential generation in neurons of the medial and lateral vestibular nuclei.

The pharmacodynamic properties of betahistine, as demonstrated in animals, may provide a positive therapeutic effect of the drug in the vestibular system.

The efficacy of betahistine has been demonstrated in clinical studies in patients with vestibular vertigo and Ménière’s disease, shown by a reduction in severity and frequency of vertigo attacks.

Pharmacokinetics.

Absorption

After oral administration, betahistine is rapidly and almost completely absorbed from the gastrointestinal tract. Following absorption, the drug is rapidly and almost entirely metabolized to form the metabolite 2-pyridylacetic acid. Plasma concentrations of betahistine are very low; therefore, all pharmacokinetic analyses are performed by measuring the concentration of the metabolite 2-pyridylacetic acid in plasma and urine.

When the drug is administered with food, the maximum concentration (Cmax) of the drug is lower compared to administration in the fasting state. However, total absorption of betahistine is identical in both cases, indicating that food intake only delays the absorption process.

Distribution

The percentage of betahistine bound to plasma proteins is less than 5%.

Biotransformation

After absorption, betahistine is rapidly and almost completely metabolized to 2-pyridylacetic acid (which has no pharmacological activity).

After oral administration, the concentration of 2-pyridylacetic acid in plasma (and in urine) reaches its maximum within 1 hour after drug intake and declines with a half-life of approximately 3.5 hours.

Elimination

2-pyridylacetic acid is rapidly excreted in urine. After administration of the drug in doses of

8–48 mg, approximately 85% of the initial dose is recovered in urine. Renal or fecal excretion of unchanged betahistine is negligible.

Linearity

The elimination rate remains constant after oral administration of 8–48 mg of the drug, indicating linear pharmacokinetics of betahistine, suggesting that the metabolic pathway involved is not saturable.

Clinical characteristics.

Indications.

Meniere's disease and Meniere's syndrome characterized by three main symptoms:

• vertigo, sometimes accompanied by nausea and vomiting;
• hearing loss (deafness);
• tinnitus.

Symptomatic treatment of vestibular vertigo of various origins.

Contraindications.

Hypersensitivity to any component of the drug.

Pheochromocytoma.

Interaction with other medicinal products and other forms of interaction.

In vivo studies on the interaction with other medicinal products have not been conducted. Based on in vitro data, inhibition of cytochrome P450 enzyme activity in vivo is not expected.

In vitro data indicate that metabolism of betahistine is inhibited by drugs that inhibit monoamine oxidase (MAO) activity, including MAO subtype B inhibitors (e.g., selegiline). Caution is recommended when administering betahistine concomitantly with MAO inhibitors (including selective MAO subtype B inhibitors).

Since betahistine is a histamine analogue, interaction between betahistine and antihistamine agents may theoretically affect the efficacy of either agent.

Special precautions for use.

Patients with bronchial asthma and/or a history of peptic ulcer of the stomach and duodenum should be carefully monitored during treatment with this medicinal product.

Use during pregnancy or breastfeeding.

Pregnancy. There is insufficient data on the use of betahistine in pregnant women.

Results of animal studies are inadequate to assess the impact on pregnancy progression, embryonic/fetal development, labour, and postnatal development. The potential risk to humans is unknown. Betahistine should not be used during pregnancy except in cases of clear necessity.

Breastfeeding period. It is unknown whether betahistine passes into human breast milk. Studies in animals on the passage of betahistine into milk have not been conducted. The benefit of treatment for the mother should be weighed against the advantages of breastfeeding and the potential risk to the infant.

Ability to influence reaction rate when driving or operating machinery.

Betahistine is indicated for the treatment of Ménière's syndrome, characterized by the triad of vertigo, hearing loss, and tinnitus, as well as for symptomatic treatment of vestibular vertigo. Both conditions may negatively affect the ability to drive or operate machinery. Clinical studies investigating the effect of the medicinal product on the ability to drive and operate machinery have shown that betahistine has no effect or only a negligible effect on this ability.

Method of administration and dosing.

The daily dose for adults is 24–48 mg, evenly divided for administration throughout the day: 1 tablet twice daily.

The drug should preferably be taken during meals or shortly after eating. The dose should be individually adjusted according to the therapeutic response. Improvement in symptoms may only become apparent after 2–3 weeks of treatment. Optimal results are achieved with continuous administration of the drug over several months. There is evidence that initiating treatment at the early stages of the disease may prevent its progression and/or hearing loss at later stages.

Geriatric patients

Although clinical data in this patient group are limited, post-marketing experience suggests that dose adjustment is not required in this population.

Renal impairment

No specific clinical trials have been conducted in patients with renal impairment; however, based on post-marketing experience, dose adjustment is not necessary.

Hepatic impairment

No specific clinical trials have been conducted in patients with hepatic impairment; however, based on post-marketing experience, dose adjustment is not necessary.

Children

Due to insufficient data on safety and efficacy, Vasoserk is not recommended for use in children (under 18 years of age).

Overdose

There have been a few reported cases of overdose. Mild to moderate symptoms (nausea, drowsiness, abdominal pain) were observed in some patients after ingestion of doses up to 640 mg. More severe complications (seizures, cardiopulmonary complications) occurred following intentional ingestion of high doses of betahistine, particularly in combination with overdose of other medicinal products.

Treatment of overdose

Management of overdose should include standard supportive measures.

Side effects.

The adverse reactions listed below were observed in patients receiving betahistine during placebo-controlled studies, with the following frequency: very common (≥ 1/10), common (≥ 1/100 to < 1/10), uncommon (≥ 1/1000 to < 1/100), rare (≥ 1/10,000 to < 1/1000), very rare (< 1/10,000).

Gastrointestinal disorders

Common: nausea and dyspepsia.

In addition to cases reported during clinical trials, the following adverse reactions have been reported spontaneously during post-marketing use and are known from scientific literature. The frequency cannot be estimated from the available data and is therefore classified as unknown.

Immune system disorders

Hypersensitivity reactions, e.g. anaphylaxis.

Gastrointestinal disorders

Reports of mild gastrointestinal disturbances (vomiting, gastrointestinal pain, bloating and flatulence). These side effects usually disappear when the medication is taken with food or after dose reduction.

Skin and subcutaneous tissue disorders

Skin and subcutaneous hypersensitivity reactions have been observed, including angioedema, rash, pruritus, and urticaria.

Shelf life. 3 years.

Storage conditions. Store at temperatures not exceeding 25°C, protected from moisture and kept out of reach of children.

Packaging.

15 tablets in a blister; 2 blisters per cardboard box.

Prescription status.

Prescription only.

Manufacturer.

ABDI IBRAHIM Ilac Sanayi ve Ticaret A.S.

Address of manufacturer and location of business operations.

Orhan Gazi Mahallesi Tunc Jaddeşi No. 3, Esenyurt/Istanbul, Turkey.