Vergostin

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT VERGOSTINE (VERGOSTINE)

Composition:

Active substance: betahistine dihydrochloride;

1 tablet contains 8 mg, 16 mg, or 24 mg of betahistine dihydrochloride;

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

Pharmaceutical form. Tablets.

Main physicochemical properties:

8 mg tablets: white or almost white, slightly mottled, round, flat, uncoated tablets with imprint «Н1» on one side and smooth on the other side;

16 mg tablets: white or almost white, slightly mottled, round, biconvex, uncoated tablets with imprint «Н2» on one side and a score line on the other side;

24 mg tablets: white or almost white, slightly mottled, round, biconvex, uncoated tablets, smooth on both sides.

Pharmacotherapeutic group.

Drugs for the treatment of the nervous system. Drugs for the treatment of vestibular disorders. Betahistine. ATC code N07CA01.

Pharmacological Properties.

Pharmacodynamics. The mechanism of action of betahistine is not fully understood. It causes an increase in blood flow in the vessels of the stria vascularis of the inner ear, primarily due to relaxation of precapillary sphincters in the microcirculatory system of the inner ear.

It has been established that betahistine has a weak agonistic effect on H1-histamine receptors and a pronounced antagonistic effect on H3-histamine receptors in the central and autonomic nervous systems. In addition, betahistine exerts a dose-dependent inhibitory effect on the generation of action potentials in neurons of the lateral and medial vestibular nuclei.

Betahistine accelerates the recovery of vestibular function after unilateral neurectomy by enhancing and facilitating the process of central vestibular compensation. This effect is characterized by enhanced regulation of histamine metabolism and release and is mediated via H3-receptor antagonism.

In combination, all these properties provide the positive therapeutic effect of betahistine in the treatment of Ménière’s disease and vestibular vertigo of various origins. Betahistine enhances histamine turnover and release by blocking presynaptic H3-receptors, thereby reducing their sensitivity. This action on the histaminergic system explains the efficacy of betahistine in treating vertigo and vestibular disorders.

Pharmacokinetics. Betahistine is rapidly and completely absorbed after oral administration in tablet form. It is excreted in the urine as 2-pyridylacetic acid within 24 hours after administration. Unchanged betahistine has not been detected. Studies using radiolabeled betahistine have shown that the plasma elimination half-life is 3–4 hours, and the urinary elimination half-life is 3–5 hours. 90% of betahistine dihydrochloride is excreted in the urine within 24 hours after administration.

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. In vitro study data allow predicting the absence of inhibition of cytochrome P450 enzyme activity in vivo.

In vitro data indicate that metabolism of betahistine is suppressed by drugs that 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 antihistaminic agents could theoretically affect the efficacy of one or both agents.

Special precautions for use

During treatment with the drug Vergostin, careful monitoring of patients with severe arterial hypotension and/or a history of peptic ulcer disease of the stomach and duodenum is necessary.

During treatment with the drug Vergostin, careful monitoring of patients with bronchial asthma, urticaria, or allergic rhinitis is required due to the risk of exacerbation of adverse symptoms.

Use during pregnancy or breastfeeding

Not recommended.

Ability to influence reaction speed when driving or operating machinery

Betahistine is indicated for the treatment of Ménière's syndrome, characterized by the classic triad of 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. According to clinical study data evaluating the drug's effect on the ability to drive and operate machinery, betahistine had no effect or only a negligible effect on this ability.

Dosage and Administration

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

8 mg tablets: 1–2 tablets three times daily;
16 mg tablets: ½–1 tablet three times daily;
24 mg tablets: 1 tablet twice daily.

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. Data suggest that initiating treatment early in the course of the disease may prevent its progression and/or hearing loss at later stages.

Geriatric patients

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

Renal impairment

Specific clinical trials have not been conducted in this patient group; however, according to post-marketing experience, dose adjustment is not necessary.

Hepatic impairment

Specific clinical trials have not been conducted in this patient group; however, according to post-marketing experience, dose adjustment is not necessary.

Children

Due to insufficient data on safety and efficacy, the drug 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, 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 when combined with overdose of other medicinal products.

Treatment. Management of overdose should include standard supportive measures.

Adverse reactions.

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

Gastrointestinal disorders

Common: nausea and dyspepsia.

Nervous system disorders

Common: headache.

In addition to the events reported during clinical trials, the following adverse reactions have been reported spontaneously during post-marketing use and in scientific literature. Based on available data, the frequency cannot be estimated reliably and is therefore classified as unknown.

Immune system disorders

Hypersensitivity reactions, e.g., anaphylaxis.

Gastrointestinal disorders

Reports of mild gastrointestinal disturbances (vomiting, gastrointestinal pain, abdominal distension and flatulence). These adverse effects usually resolve 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 angioneurotic edema, rash, pruritus, and urticaria.

Shelf life.

2 years.

Storage conditions.

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

Keep out of reach and sight of children.

Packaging.

10 tablets in a blister pack; 3 blisters per cardboard box.

Prescription status.

Prescription only.

Manufacturer.

Sun Pharmaceutical Industries Limited.

Manufacturer's address and location of business operations.

V. Ganguwala, Paonta Sahib, District Sirmour, Himachal Pradesh 173025, India.