RiteMED Betahistine

16 mg: Light pink color, round flat, scored uncoated tablets.
Each tablet contains: Betahistine Dihydrochloride 16 mg.
24 mg: Light yellow colored, round, flat, scored on one side uncoated tablets having beveled edges. The surface of the tablets may have impregnation.
Each tablet contains: Betahistine Dihydrochloride, BP 24 mg.

Pharmacotherapeutic group: Central Nervous System Antiemetic and anti-vertigo.
Pharmacology: Pharmacodynamics: 16 mg: Betahistine Dihydrochloride is an analogue of histamine. Betahistine Dihydrochloride is readily absorbed from the gastrointestinal tract. It is converted to two metabolites and peak concentrations in blood of the two metabolites are achieved within 3 to 5 hours. Most of a dose is excreted in the urine, in the form of the metabolites, in about 3 days. The mechanism of action of Betahistine is not known. Pharmacological testing in animals has shown that the blood circulation in the striae vascularis of the inner ear improves, probably by means of a relaxation of the precapillary sphincters of the microcirculation of the inner ear. In pharmacological studies, Betahistine was found to have weak H₁ receptor agonistic and considerable H₃ antagonistic properties in the central nervous system and autonomic nervous system. Betahistine was also found to have a dose dependent inhibiting effect on spike generation of neurons in lateral and medial vestibular nuclei. The importance of this observation in the action against Ménière's syndrome or vestibular vertigo, however, remains unclear.
24 mg: The mechanism of action of Betahistine is only partially understood. There are several plausible hypotheses that are supported by animal studies and human data: Betahistine affects the histaminergic system: Betahistine acts both as a partial histamine H₁-receptor agonist and histamine H₃-receptor antagonist also in neuronal tissue, and has negligible H₂-receptor activity.
Betahistine increases histamine turnover and release by blocking presynaptic H₃-receptors and inducing H₃-receptor down regulation.
Betahistine may increase blood flow to the cochlear region as well as to the whole brain: Pharmacological testing in animals has shown that the blood circulation in the striae vascularis of the inner ear improves, probably by means of a relaxation of the precapillary sphincters of the microcirculation of the inner ear.
Betahistine was also shown to increase cerebral blood flow in humans.
Betahistine facilitates vestibular compensation: Betahistine accelerates the vestibular recovery after unilateral neurectomy in animals, by promoting and facilitating central vestibular compensation; this effect is characterised by an up-regulation of histamine turnover and release, is mediated via the H₃-receptor antagonism.
In human subjects, recovery time after vestibular neurectomy was also reduced when treated with Betahistine.
Betahistine alters neuronal firing in the vestibular nuclei: Betahistine was also found to have a dose-dependent inhibiting effect on spike generation of neurons in lateral and medial vestibular nuclei.
The pharmacodynamic properties as demonstrated in animals may contribute to the therapeutic benefit of betahistine in the vestibular system.
The efficacy of betahistine was shown in studies in patients with vestibular vertigo and with Ménière's disease as was demonstrated by improvements in severity and frequency of vertigo attacks.
Mechanism of Action: Betahistine is a histamine analogue with agonist effects on H₁ receptors and antagonist on H₃. The clinical expression of this mechanism is its efficacy as an antivertiginous and to combat ringing in the ear.
At a vestibular peripheric level, Betahistine decreases the level of basal discharge of the receptors of the bulla and increases the vestibular-cochlear organs.
At a central level, Betahistine through the antagonism of H₃ autoreceptors, increases the synthesis of histamine in the tuberomammillary nucleus and release of it through the vestibular nucleus. Due to its partial agonist activity on cerebral H₁ receptors of cortical and subcortical structures, Betahistine does not affect wakefulness and even improves response capacity.
Pharmacokinetics: 16 mg: Absorption: Orally administered Betahistine is readily and almost completely absorbed from all parts of the gastrointestinal tract. After absorption, the drug is rapidly and almost completely metabolised into 2-pyridylacetic acid. Plasma levels of Betahistine are very low. Pharmacokinetic analyses are therefore based on 2-PAA measurements in plasma and urine.
Under fed conditions, C_max is lower compared to fasted conditions. However, total absorption of Betahistine is similar under both conditions, indicating that food intake only slows down the absorption of Betahistine.
Distribution: The percentage of Betahistine that is bound by blood plasma proteins is less than 5%.
Biotransformation: After absorption, Betahistine is rapidly and almost completely metabolised into 2-PAA (which has no pharmacological activity).
After oral administration of Betahistine, the plasma (and urinary) concentration of 2-PAA reaches its maximum 1 hour after intake and declines with a half-life of about 3.5 hours.
Excretion: 2-PAA is readily excreted in the urine. In the dose range between 8 and 48 mg, about 85% of the original dose is recovered in the urine. Renal or fecal excretion of Betahistine itself is of minor importance.
Linearity: Recovery rates are constant over the oral dose range of 8-48 mg indicating that the pharmacokinetics of Betahistine are linear, and suggesting that the involved metabolic pathway is not saturated.
24 mg: Absorption: Betahistine is completely absorbed after oral administration, and for fasting subjects, peak plasma concentrations of 14C-labelled betahistine are attained approximately one hour after oral administration.
Distributions: After oral administration of Betahistine, its levels in plasma are very low. Therefore, the pharmacokinetic assessment of this drug is based on plasma concentration data of the only known metabolite, 2-pyridylacetic acid. Little or binding occurs with human plasma proteins.
Metabolism and Elimination: Elimination of Betahistine primarily occurs by metabolism in the liver. Subsequently, the metabolites are mainly eliminated by renal excretion. 85-90% of the radioactivity of an 8 mg dose appears in urine over 56 hours, within 2 hours of administration. There is no evidence of presystemic metabolism, and biliary excretion is not thought to be an important route of elimination for the drug or any of its metabolites.

16 mg: Betahistine Dihydrochloride is indicated for the treatment of Ménière's syndrome or vestibular vertigo.
24 mg: Betahistine Dihydrochloride is used to reduce the symptoms of vertigo, tinnitus, and hearing loss associated with Ménière's disease.

16 mg: Adults: 8 to 16 mg three times daily taken preferably with meals. Or as prescribed by the physician.
24 mg: The usual adult initial dose is 8 to 16 mg, three times daily.
Maintenance doses are generally in the range of 24-48 mg daily.
Daily dose should not exceed 48 mg.
The dosage should be individually adapted according to the response. Improvement can sometimes only be observed after a couple of weeks of treatment.
Or as prescribed by the physician.

Overdose and Treatment: 16 mg: A few overdose cases have been reported. Some patients experienced mild to moderate symptoms with doses up to 640 mg (e.g. nausea, somnolence, abdominal pain). Other symptoms of Betahistine overdose are vomiting, dyspepsia, ataxia and seizures. More serious complications (convulsion, pulmonary or cardiac complications) were observed in cases of intentional overdose of Betahistine especially in combination with other overdosed drugs. No specific antidote. Gastric lavage and symptomatic treatment are recommended within one hour after intake.
24 mg: Symptoms: A few cases of overdosage (up to 640 mg) have been reported. In one of the cases, nausea was observed.
Treatment: Treatment should include standard supportive measures.

16 mg: Hypersensitivity to any of the ingredients.
Patients with active peptic ulcer.
Patients with Pheochromocytoma.
24 mg: Betahistine dihydrochloride is contraindicated as follows: During pregnancy and lactation.
In children less than 12 years.
Patients suffering from pheochromocytoma.
In patients with active peptic ulcer or a history of this condition.
In patients with hypersensitivity to any component of the product.

24 mg: Patients with bronchial asthma need to be carefully monitored during therapy.
Caution should be taken in the treatment of patients receiving antihistamines.

16 mg: Caution is advised in the treatment of patients with peptic ulcer or a history of peptic ulceration, because of the occasional dyspepsia encountered in patients on Betahistine.
Patients with bronchial asthma should be monitored carefully during the treatment with Betahistine.
Caution is advised in prescribing Betahistine to patients with either urticaria, rashes or allergic rhinitis, because of the possibility of aggravating these symptoms.
Caution is advised in patients with severe hypotension.
24 mg: Caution should be exercised when Betahistine dihydrochloride is given to patients with a history of peptic ulcer or asthmatic patients.
Concomitant use with antihistamines should be avoided. There is insufficient data on the use of this medicine during pregnancy and lactation.
Use in Children: 24 mg: Not recommended.
Carefully read the instructions before use.
Consult the doctor for further information.

Pregnancy: 16 mg: There is a very limited amount of data from the use of Betahistine in pregnant women. Animal studies, though insufficient do not indicate direct or indirect harmful effects with respect to reproductive toxicity. The potential risk for humans is unknown. As a precautionary measure, it is preferable to avoid the use of Betahistine during pregnancy.
24 mg: Betahistine dihydrochloride should not be used during pregnancy since there is insufficient data on the use of this drug during pregnancy to evaluate possible harmful effects. Studies in animals are inadequate or may be lacking, but available data show no evidence of an increased occurrence of fetal damage.
Lactation: 16 mg: There is insufficient information on the excretion of Betahistine in human milk. There are no animal studies on the excretion of Betahistine in milk. Betahistine should not be used during breastfeeding.
24 mg: Betahistine dihydrochloride should not be used during lactation.

The following adverse reactions have been experienced with the as follows indicated frequencies in betahistine-treated patients in placebo-controlled clinical trials [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)].
Gastrointestinal disorders: Common: nausea and dyspepsia.
Mild gastric complaints (e.g., vomiting, gastrointestinal pain, abdominal distension and bloating). These can normally be dealt with by taking the dose during meals or by lowering the dose.
Nervous system disorders: Common: headache.
In addition to those events reported during clinical trials, the following adverse reactions have been reported spontaneously during post-marketing use and in scientific literature. A frequency cannot be estimated from available data and is therefore classified as "not known".
Immune System disorders: Hypersensitivity reactions, e.g., anaphylaxis.
Skin and subcutaneous tissue disorders: Cutaneous and subcutaneous hypersensitivity reactions, in particular angioneurotic edema, urticaria, rash, and pruritus.

16 mg: There are no proven cases of hazardous interactions. No in-vivo interaction studies have been performed. Based on in-vitro data no in-vivo inhibition on Cytochrome P450 enzymes is expected.
Although an antagonism between Betahistine and antihistamines could be expected on a theoretical basis, no such interactions have been reported.
There is a case report of an interaction with ethanol and a compound containing pyrimethamine with dapsone and another of potentiation of Betahistine with salbutamol.
In vitro data indicate an inhibition of Betahistine metabolism by drugs that inhibit monoamine oxidase (MAO) including MAO subtype B (e.g. selegiline). Caution is recommended when using Betahistine and MAO inhibitors (including MAO-B selective) concomitantly.
Betahistine is a histamine analogue, concurrent administration of H₁ antagonists may cause a mutual attenuation of effect of the active agents.
24 mg: An antagonist between Betahistine dihydrochloride and antihistamine could be expected on a theoretical basis. However, no such interactions have been reported.

Store at temperatures not exceeding 30°C.

Antivertigo Drugs

N07CA01 - betahistine ; Belongs to the class of antivertigo preparations.

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