Betaserk Long, 48 mg 28 pcs

Pharmacological action

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

• Influence on the histaminergic system

Partial agonist of H1-histamine and antagonist of HZ-histamine receptors of the CNS vestibular nuclei, with little activity against H2-receptors. Betahistine increases histamine metabolism and release by blocking presynaptic NZ-receptors and decreasing the number of NZ-receptors.

• Augment blood flow to the cochlear region as well as the entire brain

According to preclinical studies, betahistine improves blood flow in the inner ear vasculature by relaxing the precapillary sphincters of the inner ear vessels. Betahistine has also been shown to increase cerebral blood flow in humans.

• Easing central vestibular compensation

Betahistine accelerates the recovery of vestibular function in animals after unilateral vestibular neurectomy by accelerating and facilitating central vestibular compensation through antagonism with NZ-histamine receptors.

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

• Inhibits neuronal excitation in the vestibular nuclei

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

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

The efficacy of betahistine has been demonstrated in patients with vestibular vertigo and Meniere’s syndrome, as evidenced by a reduction in the severity and frequency of dizziness.

Pharmacokinetics

absorption

On oral administration, betahistine is rapidly and almost completely absorbed in the gastrointestinal tract. After absorption, the drug is quickly and almost completely metabolized to form the inactive metabolite 2-pyridylacetic acid.

The plasma concentration of betahistine 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® Long, the maximum concentration (Cmax) averaged (±SD) 847 ± 147 ng/mL, time to reach maximum concentration (Tmax) was 0.333-2.0 h (median 1.0 h), time to Tlag was 0 h. The final half-life (T½) is 5.54 ± 1.57 h, the final elimination constant (λz is 0.134 ± 0.036 h-1. The total plasma exposure of 2-PAA is: AUC0-inf is 7266 ± 1338 h × ng/mL (geometric mean 7141 h × ng/mL), AUC0-τ is 7159 ± 1327 h × ng/mL (geometric mean 7035 h × ng/mL), AUC0-24, which corresponds to AUC0-τ, is 6621 ± 1111 h × ng/mL (geometric mean 6524 h × ng/mL).

The Cmax of 2-RAA was increased 1.2-fold with a single administration of Betaserc® Long compared to consecutive administration of two Betaserc® 24 mg tablets at 12-hour intervals. Tmax was increased by an average of 0.33 h when taking Betaserk® Long.

The elimination half-life of 2-PAAs when taking Betaserc® Long was on average 1.4 times longer. Total exposure averaged 0.91 of AUC0-24, 0.83 of AUC0-τ and 0.84 of AUC0-inf when taking 1 tablet of Betaserc® Long when taking 2 tablets of Betaserc® 24 mg.

A single dose of Betaserk® Long achieves a plasma exposure of 2-PAA comparable to twice-daily administration of Betaserk® 24 mg, but without a significant increase in maximum plasma concentrations.

Eating has no effect on the pharmacokinetics of 2-PAA 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).

Elimation

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

Linearity

The excretion rate remains constant with oral administration of 48 mg of the drug, indicating linearity in the pharmacokinetics of betahistine, and suggesting 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 dizziness (vertigo).

Pharmacological effect

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 H3-histamine receptors of the vestibular nuclei of the central nervous system, has little activity against H2 receptors. Betahistine increases histamine metabolism and its release by blocking presynaptic H3 receptors and reducing the number of H3 receptors.

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

According to preclinical studies, betahistine improves blood circulation in the stria vascularis of the inner ear by relaxing the precapillary sphincters of the vessels of the inner ear. Betahistine has also been shown to increase cerebral blood flow in humans.

Facilitating the process of central vestibular compensation

Betahistine accelerates the recovery of vestibular function in animals after unilateral vestibular neurectomy, accelerating and facilitating central vestibular compensation due to antagonism with H3-histamine receptors.

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

Suppression of neuronal excitation in the vestibular nuclei

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

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

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

Pharmacokinetics

Suction

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

The concentration of betahistine in 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 the drug Betaserc® Long, the maximum concentration (Cmax) is on average (±SD) 847 ± 147 ng/ml, the time to reach the maximum concentration (Tmax) is 0.333–2.0 hours (median 1.0 hours), the delay time Tlag is 0 hours. The final half-life (T½) is 5.54 ± 1.57 hours, the final elimination constant (λz – 0.134 ± 0.036 h-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, is 6621±1111 h × ng/ml (geometric mean 6524 h × ng/ml).

With a single dose of Betaserc® Long, Cmax 2-PAA increased by 1.2 times compared to sequential administration of two tablets of Betaserc® 24 mg with a 12-hour interval. Tmax when taking Betaserc® Long increased by an average of 0.33 hours.

The half-life of 2-PAA when taking Betaserc® Long increased on average by 1.4 times. The total exposure when taking 1 tablet of Betaserc® Long averages 0.91 of AUC0–24, 0.83 of AUC0–τ and 0.84 of AUC0–inf when taking 2 tablets of Betaserc® 24 mg.

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

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

Distribution

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

Metabolism

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

Removal

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 found in the urine. Excretion of betahistine by the kidneys or through the intestines is negligible.

Linearity

The rate of elimination remains constant with 48 mg of oral administration, indicating linear pharmacokinetics of betahistine and suggesting that the metabolic pathway involved remains unsaturated.

Special instructions

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

It must 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 meals.

Active ingredient

Betahistine

Composition

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

Core:

Active ingredient: betahistine dihydrochloride 24.00 mg

Excipients: Kollidon 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

Excipients: citric acid; Opadry white 03F180011 [hypromellose, titanium dioxide (E171), macrogol-6000].

Film shell (second layer of film coating (color)): Opadry II yellow 85F220031 [polyvinyl alcohol, titanium dioxide (E171), macrogol-4000, talc, iron dye yellow oxide (E172)].

Pregnancy

Pregnancy.

There is insufficient data available on the use of betahistine in pregnant women. Animal studies have shown no direct or indirect reproductive toxicity. Betahistine should not be used during pregnancy unless clearly needed.

Breast-feeding.

It is unknown whether betahistine is excreted in human breast milk. Betahistine is excreted in breast milk in rats. Animal studies have been limited to very high doses of the drug. The question of prescribing a drug to the mother should be made only after comparing the benefits of breastfeeding with the potential risk to the infant.

Fertility.

Animal studies (rats) have not shown any effect on fertility.

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.
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, gastric and/or duodenal ulcers require careful monitoring during treatment.

Side Effects

Common: nausea and dyspepsia; headache;

Not known: hypersensitivity reactions, including anaphylactic reaction, vomiting, gastrointestinal pain, bloating, angioedema, urticaria, itching, rash.

Interaction

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

Based on in vitro data, it can be assumed that there is no inhibition of the activity of isoenzymes of the cytochrome P450 system in vivo.

In vitro data have shown inhibition of betahistine metabolism by drugs that inhibit MAO, including MAO subtype B (eg, selegiline). Caution should be exercised when prescribing betahistine and MAO inhibitors (including MAO-B) simultaneously.

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

The patient should tell the doctor if they are currently or recently taking any medications.

Overdose

There are several known cases of overdose of 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 (convulsions, cardiopulmonary complications) have been observed with deliberate use of betahistine in increased doses, especially in combination with overdose of other drugs.

Treatment: symptomatic therapy.

Storage conditions

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

Shelf life

1 year

Manufacturer

Veropharm LLC, Russia