Betaserk Long, 48 mg 56 pcs.

Pharmacotherapeutic group: histamine drug

ATC code: N07CA01

Pharmacological properties

.Pharmacodynamics

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 H3-histamine receptors of the CNS vestibular nuclei, with little activity against
H2-receptors. Betahistine increases histamine metabolism and release by blocking presynaptic H3 receptors and decreasing H3 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 vestibular function recovery in animals after unilateral vestibular neurectomy by accelerating and facilitating central vestibular compensation through antagonism with H3-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

. 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 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 (C_max) averages (±SD) 847±147 ng/mL, time to maximum concentration (T_max) is 0.333-2.0 h (median 1.0 h), time to latency T_lag is 0 h. The terminal elimination half-life (T_1/2) is 5.54±1.57 h, the terminal elimination constant (λ_z) is 0.134±0.036 h^-1. The total plasma exposure of 2-PAA is: AUC_0-inf – 7266±1338 h×ng/mL (geometric mean 7141 h×ng/mL), AUC_0-t – 7159±1327 h×ng/mL (geometric mean 7035 h×ng/mL), AUC_0-24, corresponding to an AUC_0-t, of 6621±111111 h×ng/mL (geometric mean 6524 h×ng/mL).

A single administration of Betaserc^® Long C_max 2-RAA increased 1.2-fold compared with consecutive administration of two Betaserc^® 24 mg tablets at
12-hour intervals. T_max when taking Betaserc^® Long is increased by an average of 0.33 h. The elimination half-life of 2-PAAs while taking Betaserc^® Long increased by an average of 1.4 times. Total exposure when taking 1 tablet of Betaserc^® Long averaged 0.91 of the AUC_0-24, 0.83 of the AUC_0-t and 0.84 of the AUC_0-inf when taking 2 tablets of Betaserc^® 24 mg.

The administration of a single dose of Betaserc^® Long achieves plasma 2-PAA exposure comparable to twice-daily administration of Betaserc^® 24 mg, but without significantly increasing 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

Menière syndrome, characterized by the following main symptoms:

• dizziness (accompanied by nausea/vomiting)
• decreased hearing (hearing loss)
• tinnitus

Symptomatic treatment of vestibular vertigo (vertigo).

Active ingredient

Betahistine

Composition

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

nucleus:

Activeparticle: betahistine dihydrochloride 24.00 mg

Associated substances: collidone SR, microcrystalline cellulose 102, lactose monohydrate, citric acid, magnesium stearate, talc.

Film shell (first layer film coatingfilm coating):

Active substance: betahistine dihydrochloride 24.00 mg

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

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

How to take, the dosage

Internal. With meals.

The Betaserk^® Long tablet must not be divided into portions because it is coated with a film to allow gradual release of the active ingredient.

The dose of Betaserc^® Long for adults is:

1 tablet daily in the morning.

Elderly age

Despite limited clinical trial data, extensive post-registration experience suggests that dose adjustments are not necessary in this patient group.

Patients with renal/hepatic impairment

Special clinical studies have not been performed in this patient group, but post-registration experience suggests that no dose adjustment is necessary in this patient group.

Interaction

If you are currently or have recently taken other medicines, including non-prescription medicines, please tell your physician.

There have been no in vivo studies looking at interactions with other medicinal products. Based on the in vitro data, it can be assumed that there is no inhibition of cytochrome P450 isoenzyme activity in vivo.

The in vitro data showed inhibition of betahistine metabolism by drugs that inhibit monoamine oxidase (MAO), including MAO subtype B (such as selegiline). Caution should be exercised when using betahistine and MAO inhibitors (including MAO-B) concomitantly.

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

Special Instructions

Influence on driving and operating ability

Betahistine has no or negligible effect on driving and operating machinery, no adverse reactions that could affect such ability have been identified in clinical trials.

Synopsis

Round biconvex tablets, covered with an upper film coating of brownish-yellow color. On cross section the pill core is white to white with yellow tinge, the first layer of the film coating is white.

Contraindications

• High sensitivity to any of the ingredients
• Lactose intoleranceLactose intolerance, lactase deficiency and glucose-galactose malabsorption due to the presence of lactose in the drug
• Pheochromocytoma
• Pheochromocytoma

Not recommended for use in children under 18 years of age due to insufficient efficacy and safety data

Cautions

Patients with bronchial asthma, peptic ulcer disease and/or duodenal disease require close monitoring during treatment.

Side effects

The following are the adverse drug reactions (ADRs) that occurred during the use of the drug in clinical trials, with an indication of their frequency of occurrence. They are grouped according to the MedDRA Organ and Organ System Classification.

The frequency of occurrence is defined as follows: very common (≥1/10), frequent (≥1/100 and < 1/10), not common (≥1/1000 and < 1/100), frequently (≥ 1/10000 and < 1/1000), very rarely (< 1/10000, including individual cases).

Nervous system disorders:often: headache.

Gastrointestinal tract disorders:often: nausea and dyspepsia.

When taking Betaserk^® Long, gastrointestinal and central nervous system adverse events (headache) developed with less frequency, which was statistically confirmed by an additional analysis in a clinical trial of the efficacy and safety of Betaserc^® Long.

In addition to these effects identified in clinical studies, the following adverse effects have been reported during post-registration use of betahistine and in the scientific literature. There is insufficient data available to estimate their frequency.

Immune system disorders:Hypersensitivity reactions, including anaphylactic reactions.

Gastrointestinal disorders:moderate disorders such as vomiting, gastrointestinal pain, bloating. These effects usually disappear after taking the drug at the same time as food.

Skin and subcutaneous tissue disorders:Skin and subcutaneous tissue hypersensitivity reactions, particularly angioedema, itching, and rash.

If any of the side effects listed in the instructions worsen, or if you notice any other side effects not mentioned in these instructions, or if any side effect becomes serious, please notify Your doctor.