Betaserc Long modified-release pills 48mg, 28pcs

Composition

1 modified release film-coated tablet,48 mg, contains:

Core:

Active ingredient:  betahistine dihydrochloride 24.00 mg

Auxiliary substances:  collidone SR [polyvinyl acetate, povidone-KZO, sodium lauryl sulfate, silicon dioxide], microcrystalline cellulose 102, lactose monohydrate, citric acid, magnesium stearate, talc.

Film shell (first layer of film coating):

Active ingredient:  betahistine dihydrochloride 24.00 mg

Auxiliary substances:  citric acid; Opadray white 03F180011 [hypromellose, titanium dioxide (E171), macrogol-6000]. Film shell (second layer of film coating (color)):  Opadray II yellow 85F220031 [polyvinyl alcohol, titanium dioxide (E171), macrogol-4000, talc, iron oxide yellow dye (E172)].

Pharmacological action

Pharmacological action

The mechanism of action of betahistine is only partially known. There are several possible hypotheses supported by preclinical and clinical data:

• Effect on the histaminergic system

Partial agonist of H1-histamine and antagonist of NC-histamine receptors of the vestibular nuclei of the central nervous system, has little activity against H2-receptors. Betahistine increases histamine metabolism and release by blocking presynaptic NC receptors and reducing the number of NC receptors.

• Increased blood flow to the cochlear region, as well as the entire brain

According to preclinical studies, betahistine improves blood circulation in the vascular strip of the inner ear by relaxing the precapillary sphincters of the inner ear vessels. Betahistine has also been shown to increase blood flow to the human brain.

• Facilitating the central vestibular compensation process

Betahistine accelerates the restoration of vestibular function in animals after unilateral vestibular neurectomy, accelerating and facilitating central vestibular compensation due to antagonism with NC-histamine receptors.

Recovery time after vestibular neurectomy in humans with betahistine treatment is also reduced.

• Suppression of neuronal firing in the vestibular nuclei

Dose-dependently reduces the generation of action potentials in neurons of the lateral and medial vestibular nuclei.

Pharmacodynamic properties revealed in animals provide a positive therapeutic effect of betahistine in the vestibular system.

The efficacy of betahistine was demonstrated in patients with vestibular vertigo and Meniere’s syndrome, which was manifested by a decrease in the severity and frequency of vertigo.

Pharmacokinetics

Suction

When taken orally, betahistine is rapidly and almost completely absorbed in the gastrointestinal tract. After absorption, the drug is rapidly and almost completely metabolized to form an inactive metabolite of 2-pyridylacetic acid.

The concentration of betahistine in the blood plasma is very low. Thus, pharmacokinetic assays are based on measuring the concentration of the metabolite 2-pyridylacetic acid (2-PAA) in plasma and urine.

For Betaserc® The long maximum concentration (Cmax) is on average (±SD) 847 ± 147 ng / ml, the time to reach the maximum concentration (Tmax) is 0.333-2.0 h (median 1.0 h), and the Tlag delay time is 0 h. The final half-life (half-life) is 5.54 ± 1.57 hours, the final elimination constant (λz-0.134 ± 0.036 hours-1. The total exposure of 2-PAA in blood plasma is: AUC0-inf-7266±1338 h × ng/ml (geometric mean 7141 h × ng / ml), AUC0–τ — 7159 ± 1327 h × ng/ml (geometric mean 7035 h × ng/ml), AUC0–24, which corresponds to AUC0–τ — 6621±1111 h × ng/ml (geometric mean 6524 h × ng/ml).

With a single dose of Betaserc® Long-term Cmax of 2-RAA increased 1.2-fold compared to consecutive use of two tablets of Betaserc® 24 mg at 12-hour intervals. Tmax when taking Betaserc® Long on average increased by 0.33 hours.

Half-life of 2-RAA when taking Betaserc® On average, the long term increased by 1.4 times. Total exposure when taking 1 tablet of Betaserc® Long is on average 0.91 of AUC0-24,0.83 of AUC0-t and 0.84 of AUC0-inf when taking 2 tablets of Betaserc® 24 mg.

When taking a single dose of Betaserc® Long-term exposure of 2-RAA in blood plasma is achieved, comparable to a double dose of Betaserc® 24 mg, but without a significant increase in the maximum concentration in blood plasma.

Food intake does not affect the pharmacokinetics of 2-RAA when taking Betaserc® Long.

Distribution

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

Metabolism

After absorption, betahistine is rapidly and almost completely metabolized to form the metabolite 2-PAA (which has no pharmacological activity).

2-PAA is rapidly excreted in the urine. When taking the drug at a dose of 48 mg, about 85% of the initial dose is detected in the urine. Elimination of betahistine by the kidneys or through the intestines is insignificant.

Linearity

The rate of elimination remains constant with oral use of 48 mg of the drug, indicating the linearity of the pharmacokinetics of betahistine, and suggests that the metabolic pathway involved remains unsaturated.

Indications

• Meniere’s syndrome, characterized by the following main symptoms: dizziness (accompanied by nausea/vomiting); hearing loss (hearing loss); tinnitus.
• symptomatic treatment of vestibular vertigo (vertigo).

Use during pregnancy and lactation

Pregnancy.

The available data on the use of betahistine in pregnant women are insufficient. Animal studies have shown no direct or indirect reproductive toxicity. Betahistine should not be used during pregnancy unless absolutely necessary.

Breast-feeding.

It is not known whether betahistine is excreted in human breast milk. Betahistine is excreted in human milk in rats. Animal studies have been limited to the use of the drug in very high doses. The question of prescribing a drug to the mother should be decided only after comparing the benefits of breastfeeding with the potential risk to the infant.

Fertility.

In animal studies (rats), no effect on fertility was found.

Contraindications

• Hypersensitivity to any of the components of the drug.
• Lactose intolerance, lactase deficiency and glucose-galactose malabsorption due to the presence of lactose in the drug.
• Pheochromocytoma.
• It is not recommended for use in children under 18 years of age due to insufficient data on efficacy and safety.

With caution

Patients with bronchial asthma, stomach and/or duodenal ulcers require careful monitoring during treatment.

Side effects

Common: nausea and dyspepsia; headache; Frequency unknown: hypersensitivity reactions, including anaphylactic reaction, vomiting, gastrointestinal pain, bloating, angioedema, urticaria, pruritus, rash.

Interaction

In vivo studies aimed at studying the interaction with other drugs have not been conducted.

Based on in vitro data, it can be assumed that the activity of cytochrome P450 isoenzymes is not inhibited in vivo.

In vitro data showed inhibition of betahistine metabolism by drugs that inhibit MAO, including MAO subtype B (for example, selegiline). Caution should be exercised when concomitantly prescribing betahistine and MAO inhibitors (including MAO-B).

Betahistine is a histamine analog, and the interaction of betahistine with H1-histamine receptor blockers can theoretically affect the effectiveness of one of these drugs.

The patient should inform the doctor about taking any medications currently or in the recent past.

How to take, course of use and dosage

Inside. While eating.

The Betaserc®tablet Long can not be divided into parts, as it is covered with a film shell in order to gradually release the Active ingredient.

Betaserc®Dose Long for adults is: 1 tablet daily in the morning.

Advanced age

Despite limited data from clinical trials, extensive post-marketing experience suggests that dose adjustment is not required in this group of patients.

Patients with renal / hepatic insufficiency

No specific clinical studies have been conducted in this group of patients, but post-marketing experience suggests that dose adjustment is not required in this category of patients.

Overdose

There are several known cases of overdose of the drug Betaserc.

Symptoms: mild to moderate nausea, drowsiness, abdominal pain were observed in some patients after taking the drug in doses up to 640 mg.

More serious complications (seizures, cardiopulmonary complications) were observed with deliberate use of betahistine in increased doses, especially in combination with an overdose of other medications.

Treatment: performing symptomatic therapy.

Special instructions

It should be used with caution in patients with a history of gastric or duodenal ulcer, in the second and third trimesters of pregnancy, as well as in children.

It should be taken into account that the desired clinical effect is achieved after several months of treatment.

For dyspeptic symptoms, betahistine is recommended to be taken during or after a meal.

Form of production

Tablets

Storage conditions

In a dry place, at a temperature not exceeding 25 °C

Shelf life

1 year

Active ingredient

Betahistine

Conditions of release from pharmacies

By prescription

Dosage form

Tablets