Vestinorm

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

Composition:

Active substance: betahistine;

One tablet contains 8 mg, 16 mg, or 24 mg of betahistine dihydrochloride, calculated as 100% dry substance;

Excipients: microcrystalline cellulose, sodium starch glycolate (type A), colloidal anhydrous silicon dioxide, povidone, magnesium stearate.

Pharmaceutical form. Tablets.

Main physicochemical properties: round, flat-faced tablets with a bevel and a score line, white or almost white in color. Marbling on the surface of the tablets is permissible (for 8 mg and 16 mg tablets).

Pharmacotherapeutic group. Agents for the treatment of vestibular disorders.

ATC Code N07CA01.

Pharmacological properties.

Pharmacodynamics.

The mechanism of action of betahistine is only partially understood. There are several plausible hypotheses that have been supported by data from studies conducted in animals and 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 negligible activity at histamine H2-receptors. Betahistine increases histamine turnover and release by blocking presynaptic H3-receptors and inducing down-regulation of these H3-receptors.

Betahistine may increase blood flow in the cochlear region as well as in 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 the recovery of vestibular function after unilateral neurectomy in animals by stimulating and supporting the process of central vestibular compensation. This effect is characterized by enhanced regulation of histamine turnover and release, mediated through H3-receptor antagonism. In humans, treatment with betahistine has also been associated with a reduced time for vestibular function recovery 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 generation in neurons of the lateral and medial vestibular nuclei.

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

The efficacy of betahistine has been demonstrated in clinical studies in patients with vestibular vertigo and Ménière’s disease, as 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 quickly 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 administered with food, the maximum concentration (Cmax) of the drug is lower than when administered fasting. 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 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 after oral doses of 8–48 mg, indicating linear pharmacokinetics of betahistine, and suggests 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 aimed at investigating interactions 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 the metabolism of betahistine may be inhibited by drugs which inhibit monoamine oxidase (MAO) activity, including MAO subtype B (e.g., selegiline). Caution is recommended when administering betahistine concomitantly with MAO inhibitors (including selective inhibitors of MAO subtype B).

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

Special precautions for use.

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

Caution is recommended when using the drug in patients with peptic ulcer disease (including in medical history), as cases of dyspepsia occasionally occur in patients taking betahistine.

Betahistine should be prescribed with caution to patients with existing urticaria, rash, or allergic rhinitis, as these symptoms may worsen.

The drug should be prescribed with caution to patients with severe hypotension.

Use during pregnancy or breastfeeding.

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

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

Lactation 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. Betahistine should not be used during breastfeeding.

Ability to influence reaction rate while driving or operating machinery.

Dizziness, hearing loss, and tinnitus associated with Ménière's syndrome may negatively affect the ability to drive or operate machinery. According to clinical trial data, betahistine does not exert a significant effect or produce effects that could potentially impair the ability to drive a vehicle or operate machinery.

Dosage and Administration.

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

The dose should be individually adjusted according to the effect. Improvement of symptoms is sometimes observed only after 2–3 weeks of treatment. The best results are sometimes achieved with administration of the drug for several months. There is evidence that initiating treatment at an early stage of the disease prevents its progression and/or hearing loss at later stages.

Elderly patients

Although clinical trial data in this patient group are limited, extensive post-marketing experience suggests that dose adjustment is not required for this category of patients.

Renal impairment

No specific clinical trials have been conducted in this patient group, but according to post-marketing experience, dose adjustment is not required.

Hepatic impairment

No specific clinical trials have been conducted in this patient group, but according to post-marketing experience, dose adjustment is not required.

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

Overdose.

There have been several reported cases of overdose. In some patients, mild to moderate symptoms were observed after doses up to 640 mg (nausea, drowsiness, abdominal pain). Other symptoms of overdose included vomiting, dyspepsia, ataxia, and seizures. More severe complications (convulsions, cardiac and pulmonary complications) were observed following intentional ingestion of high doses of betahistine, particularly when combined with overdose of other medicinal products.

Treatment: gastric lavage and symptomatic therapy are recommended within one hour after drug intake.

Side effects.

Gastrointestinal tract: nausea and dyspepsia, complaints of mild stomach disturbances (vomiting, gastrointestinal pain, abdominal distension 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: hypersensitivity reactions of the skin and subcutaneous fatty tissue, including angioneurotic edema, rash, pruritus, and urticaria.

Shelf life.

3 years.

Do not use the medication after the expiry date stated on the packaging.

Storage conditions.

Store in a light-protected place at a temperature not exceeding 25 °C.

Keep out of reach of children.

Packaging. 10 tablets per blister. 8 mg tablets. 3 blisters per pack.

16 mg and 24 mg tablets. 3 or 6 blisters per pack.

Prescription status. Prescription only.

Manufacturer.

JSC "Farmak".

Manufacturer's address and place of business.

74, Kyrylivska Street, Kyiv, 04080, Ukraine.