Betahistin-kv

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT BETAHISTINE-KV (BETAHISTINE-KV)

Composition:

Active substance: betahistine dihydrochloride;

One tablet contains betahistine dihydrochloride equivalent to 100% substance 8 or 16 or 24 mg;

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

Pharmaceutical form. Tablets.

Main physico-chemical properties:

tablets 8 mg: flat cylindrical tablets, bevelled edges, white or almost white. Marbling on the surface of the tablets is permissible;

tablets 16 mg or 24 mg: flat cylindrical tablets, with bevelled edges and a score line, white or almost white. Marbling on the surface of the tablets is permissible.

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. It is known that several plausible hypotheses have been confirmed by studies conducted in animals and humans.

Effect of betahistine on the histaminergic system.

It has been established that betahistine exhibits partial agonist activity at H1-histamine receptors and antagonist activity at H3-histamine receptors in nervous tissue, with negligible activity at H2-histamine receptors. Betahistine increases histamine turnover and release by blocking presynaptic H3-receptors and inducing a down-regulation process of corresponding H3-receptors.

Betahistine may increase blood flow in the cochlear region as well as in the entire brain.

There is evidence of 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 demonstrated an increase in cerebral blood flow in humans.

Betahistine promotes vestibular compensation.

Betahistine accelerates the recovery of vestibular function after unilateral neurectomy in animals, stimulating and supporting 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 vestibular nuclei.

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

It is known that the pharmacodynamic properties of betahistine may provide a positive therapeutic effect on 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 the severity and frequency of vertigo attacks.

Pharmacokinetics.

Absorption. After oral administration, betahistine is rapidly and almost completely absorbed throughout the gastrointestinal tract. Following absorption, the drug is rapidly and almost entirely metabolized to the metabolite 2-pyridylacetic acid. Plasma concentrations of betahistine itself 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 taken with food, the maximum concentration (Cmax) of the drug is lower than when taken on an empty stomach. However, the 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 of betahistine, the concentration of 2-pyridylacetic acid in plasma (and 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 betahistine 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 rate of elimination remains constant following oral doses of 8–48 mg of the drug, indicating linear pharmacokinetics of betahistine, and 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 medicinal product. Pheochromocytoma.

Interaction with other medicinal products and other forms of interaction.

In vivo studies specifically designed to investigate interactions with other medicinal products have not been conducted. Based on in vitro data, inhibition of cytochrome P450 enzyme activity is not expected in vivo.

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

Since betahistine is a histamine analogue, interaction between betahistine and antihistamines may theoretically affect the efficacy of one or both agents.

Special precautions for use.

During treatment with the medicinal product, patients with bronchial asthma and/or a history of peptic ulcer of the stomach and duodenum should be carefully monitored.

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 effect on pregnancy course, embryo/fetal development, parturition, and postnatal development. The potential risk for 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 affect reaction rate while driving or operating machinery.

Betahistine is indicated for the treatment of Ménière's syndrome, characterized by the triad of main symptoms: 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. It is known that betahistine does not affect or has negligible effects on the ability to drive a vehicle or operate machinery.

Method of administration and dosage.

The daily dose for adults is 24–48 mg, evenly divided and administered throughout the day.

The dose should be individually adjusted depending on the effect. Improvement of symptoms is sometimes observed only after two to three weeks of treatment. The best results are sometimes achieved with administration of the medicinal product for several months. There is evidence that initiating treatment at an early stage of the disease may prevent its progression and/or hearing loss at later stages.

Geriatric patients

Post-marketing experience suggests that dose adjustment is not required for this patient population.

Renal impairment

Post-marketing experience indicates that dose adjustment is not required.

Hepatic impairment

Post-marketing experience indicates that dose adjustment is not required.

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

Overdose.

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

Treatment of overdose should include standard supportive measures.

Side effects.

Gastrointestinal tract: nausea and dyspepsia, mild stomach disturbances (vomiting, gastrointestinal pain, bloating and flatulence). These adverse effects usually resolve when the medication is taken with food or after dose reduction.

Nervous system: headache.

Immune system: hypersensitivity reactions, for example anaphylaxis.

Skin and subcutaneous tissue: skin and subcutaneous fat tissue hypersensitivity reactions have been observed, including angioedema, rash, pruritus and urticaria.

Shelf life. 3 years.

Storage conditions.

Store in the original packaging at a temperature not exceeding 25 °C.

Keep out of the reach of children.

Packaging.

10 tablets in a blister pack, 3 blisters in a carton.

Prescription status. Prescription only.

Manufacturer.

JSC "KYIV VITAMIN PLANT".

Manufacturer's location and address of its business activity.

38 Kopilivska Street, Kyiv, 04073, Ukraine.

Web-site: www.vitamin.com.ua.