Instructions for use Medogistin tablets 16 mg blister No. 30
Composition
active ingredient: betahistine dihydrochloride;
1 tablet contains betahistine dihydrochloride 16 mg or 24 mg;
Excipients: lactose monohydrate; corn starch; microcrystalline cellulose; citric acid anhydrous; povidone; crospovidone; hydrogenated vegetable oil.
Dosage form
Pills.
Main physicochemical properties:
16 mg tablets: white or almost white, flat, round tablets, with a bevel and a score, approximately 9 mm in diameter;
24 mg tablets: white or almost white, flat, round tablets with a bevel and a score, approximately 10 mm in diameter.
Pharmacotherapeutic group
Means for the treatment of vestibular disorders. ATX code N07C A01.
Pharmacological properties
Pharmacodynamics.
The mechanism of action of betahistine is only partially understood. There are several plausible hypotheses supported by animal and human studies.
The effect of betahistine on the histaminergic system. It has been established that betahistine partially exhibits agonistic activity at H1 receptors, as well as antagonistic activity at H3 histamine receptors in nervous tissue and has little activity at H2 histamine receptors. Betahistine increases the metabolism and release of histamine by blocking presynaptic H3 receptors and inducing a process of decreasing the number of corresponding H3 receptors.
Betahistine can increase blood flow to the cochlear area as well as to the entire brain. Pharmacological studies in animals have shown an improvement in blood flow in the stria vascularis of the inner ear, possibly by relaxing precapillary sphincters in the inner ear microcirculation system. 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 nephrectomy in animals, accelerating and facilitating the process of central vestibular compensation. This effect is characterized by increased regulation of histamine metabolism and release and is realized as a result of H3-receptor antagonism. In humans, treatment with betahistine also reduced the time to recovery of vestibular function after neurectomy.
Betahistine alters the activity of neurons in the vestibular nuclei. It has also been found that betahistine exerts a dose-dependent inhibitory effect on the generation of spike potentials in neurons of the lateral and medial vestibular nuclei.
The pharmacodynamic properties of betahistine, as shown in animals, may provide a positive therapeutic effect of the drug in the vestibular system. Betahistine has been shown to be effective in studies in patients with vestibular vertigo and Ménière's disease, as evidenced by a reduction in the severity and frequency of vertigo attacks.
Pharmacokinetics.
Absorption. When administered orally, betahistine is rapidly and almost completely absorbed from the gastrointestinal tract. After absorption, the drug is rapidly and almost completely metabolized to form the metabolite 2-pyridylacetic acid. The concentration of betahistine in blood plasma is very low. Therefore, all pharmacokinetic analyses are carried out by measuring the concentration of the metabolite 2-pyridylacetic acid in blood plasma and urine.
When taking the drug with food, the maximum concentration (Cmax) of betahistine is lower than when taken on an empty stomach. At the same time, the complete absorption of betahistine is identical in both cases. Therefore, food intake only slows down the absorption process of the drug.
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 the blood plasma (and urine) reaches its maximum 1 hour after administration and decreases with a half-life of about 3.5 hours.
Excretion. 2-pyridylacetic acid is rapidly excreted in the urine. When taking the drug in a dosage of 8-48 mg, about 85% of the initial dose is found in the urine. The excretion of betahistine by the kidneys or with feces is insignificant.
Linearity. The recovery rate remains constant over the oral administration of 8-48 mg of the drug, indicating linearity of the pharmacokinetics of betahistine and suggesting that the metabolic pathway involved remains non-intensive.
Indication
Meniere's disease and syndrome, which are characterized by three main symptoms:
dizziness, sometimes accompanied by nausea and vomiting;
hearing loss (hearing loss);
tinnitus.
Symptomatic treatment of vestibular vertigo of various origins.
Contraindication
Hypersensitivity to any of the components of the drug. Pheochromocytoma.
Interaction with other medicinal products and other types of interactions
In vivo drug interaction studies have not been performed. Based on in vitro data, inhibition of cytochrome P450 enzyme activity in vivo is not expected. In vitro data indicate inhibition of betahistine metabolism by drugs that inhibit monoamine oxidase (MAO) activity, including MAO subtype B (e.g. selegiline). Caution is recommended when betahistine is co-administered with MAO inhibitors (including MAO subtype B). Since betahistine is a histamine analogue, the interaction of betahistine with antihistamines could theoretically affect the efficacy of one of these drugs.
Application features
During treatment with Medogistin®, it is necessary to carefully monitor the condition of patients with bronchial asthma and/or a history of gastric and duodenal ulcers. The drug contains lactose, so it should not be used in patients with rare hereditary forms of galactose intolerance, lactase deficiency or glucose-galactose malabsorption syndrome.
Use during pregnancy or breastfeeding
Pregnancy: There are no adequate data from the use of betahistine in pregnant women. Animal studies do not indicate direct or indirect harmful effects with respect to reproductive toxicity at doses similar to those used in clinical practice. Betahistine should not be used during pregnancy unless clearly necessary.
Breastfeeding. It is not known whether betahistine is excreted in human milk. Betahistine is excreted in rat milk. Effects observed after delivery in animal studies were only observed at very high doses. The benefit of the drug to the mother should be weighed against the benefits of breastfeeding and the potential risk to the child.
Fertility: Studies in rats have shown no effect on fertility.
The ability to influence the reaction speed when driving or working with other mechanisms
Betahistine is indicated for the treatment of Ménière's syndrome and for the symptomatic treatment of vestibular vertigo. Both conditions may adversely affect the ability to drive and use machines. In clinical studies on the effects of the drug on the ability to drive and use machines, betahistine had no or negligible influence on this ability.
Method of administration and doses
The daily dose for adults is 24-48 mg, evenly distributed throughout the day.
| 16 mg tablets | 24 mg tablets |
| ½-1 tablet 3 times a day | 1 tablet 2 times a day |
The dose should be adjusted individually, depending on the effect. A reduction in symptoms is sometimes observed only after several weeks of treatment. The best results are achieved when the drug is taken for several months. There is evidence that prescribing treatment early in the disease prevents its progression and/or hearing loss in the later stages.
The tablets should be swallowed with water, regardless of meals.
Elderly patients: Although clinical trial data in this patient population are currently limited, extensive post-marketing experience suggests that no dose adjustment is necessary for this patient population.
Renal insufficiency. Special clinical trials have not been conducted in this group of patients, but based on post-marketing experience, no dose adjustment is required.
Hepatic insufficiency. Special clinical trials have not been conducted in this group of patients, but based on post-marketing experience, no dose adjustment is required.
Children
Due to insufficient data on the safety and efficacy of the drug Medogistin®, it is not recommended to prescribe it to children (under 18 years of age).
Overdose
Several cases of overdose of the drug are known. Some patients experienced mild to moderate symptoms (nausea, drowsiness, abdominal pain) after taking the drug in doses up to 640 mg. More serious complications (convulsions, cardiopulmonary complications) were observed with intentional administration of increased doses of betahistine, especially in combination with an overdose of other drugs. Treatment of overdose should include symptomatic therapy.
Side effects
The following adverse reactions are classified according to the following frequency: 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), frequency unknown (cannot be estimated from the available data).
Gastrointestinal disorders: Common: nausea and dyspepsia.
Nervous system disorders: Common: headache.
In addition to cases reported during clinical trials, the following adverse reactions have been reported spontaneously during post-marketing use and in the scientific literature. The frequency cannot be estimated from the available data and is therefore classified as not known.
Gastrointestinal: Frequency unknown: complaints of minor stomach upset (vomiting, pain in the gastrointestinal tract, flatulence). These side effects usually disappear when the drug is taken with food or after reducing the dose.
Skin and subcutaneous tissue disorders: Hypersensitivity reactions of the skin and subcutaneous tissue, including angioedema, rash, pruritus and urticaria, have been observed.
Reporting of suspected adverse reactions. Reporting of adverse reactions after registration of a medicinal product is important. This allows monitoring of the benefit/risk ratio of the medicinal product. Medical and pharmaceutical professionals, as well as patients or their legal representatives, should report all cases of suspected adverse reactions and lack of efficacy of the medicinal product via the Automated Information System for Pharmacovigilance at the following link: https://aisf.dec.gov.ua/
Expiration date
3 years.
Storage conditions
Store at a temperature not exceeding 25 °C in the original packaging, out of the reach of children.
Packaging
10 tablets in a blister; 3 blisters in a cardboard box.
Vacation category
According to the recipe.
Producer
1. Medochemie LTD (Central Factory).
2. Pharmaceutical Analytical Laboratory Duiven B.V.
Location of the manufacturer and its business address
1. 1-10 Constantinoupoleos Street, Limassol, 3011, Cyprus.
2. Dijkgraaf 30, Duiven, 6921RL, Netherlands.
