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

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

Active ingredient

Betahistine

Composition

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

Core:

The active ingredient: betahistine dihydrochloride 24.00 mg

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

The film coating (first layer of film coating):

The active ingredient: betahistine dihydrochloride 24.00 mg

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

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

How to take, the dosage

Internal. With meals.

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

The dose of Betaserk® Long for adults is: 1 tablet daily in the morning.

Elderly age

Although data from clinical studies are limited, extensive post-registration experience suggests that no dose adjustment is necessary in this patient group.

Patients with renal/hepatic impairment

Dedicated 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

In vivo studies to study the interaction with other drugs have not been conducted.

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

In vitro data showed inhibition of betahistine metabolism by drugs that inhibit MAOIs, including MAO subtype B (e.g., selegiline). Caution should be exercised when concomitant administration of betahistine and MAO inhibitors (including MAO-B).

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

The patient must tell the physician if he or she is currently taking any medications, or has taken any medications in the recent past.

Special Instructions

Caution should be exercised in patients with a history of gastric or duodenal ulcer disease, in the second and third trimesters of pregnancy, and in children.

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

In case of dyspeptic symptoms, betahistine is recommended to be taken with or after meals.

Contraindications

• High sensitivity to any of the ingredients.
• 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 efficacy and safety data.

Cautions

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

Side effects

Frequently: nausea and dyspepsia; headache;

Frequency unknown: hypersensitivity reactions, including anaphylactic reaction, vomiting, gastrointestinal pain, abdominal bloating, angioedema, urticaria, itching, rash.

Overdose

There have been several known cases of overdose of Betaserc.

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

More serious complications (seizures, cardiopulmonary complications) have been observed when betahistine is intentionally taken at higher doses, especially in combination with overdose of other medications.

Treatment: conduct symptomatic therapy.

Pregnancy use

Pregnancy.

The data available 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 clearly necessary.

Breastfeeding.

It is not known whether betahistine is excreted with breast milk in humans. Betahistine is excreted with breast milk in rats. Animal studies have been limited to the use of the drug at very high doses. Administration of the drug to the mother should be decided only after weighing the benefits of breastfeeding against the potential risks to the infant.

Fertility.

There has been no effect on fertility in animal studies (rats).

Similarities

Betaserk, Vestibo, Betahistine, Betahistine NW, Tagista, Vertran