Betahistine is indicated for treatment of Ménière's syndrome, symptoms of which may include vertigo, tinnitus, hearingloss and nausea.

Adults

Initial oral treatment is 8 to 16 mg three times daily, taken preferably with meals.

Maintenance doses are generally in the range 24 - 48 mg daily. Daily dose should not exceed 48 mg. Dosage can be adjusted to suit individual patient needs. Sometimes improvement could be observed only after a couple of weeks of treatment.

Renal impairment

There are no specific clinical trials available in this patient group, but according to post-marketing experience no dose adjustment appears to be necessary.

Hepatic impairment

There are no specific clinical trials available in this patient group, but according to post-marketing experience no dose adjustment appears to be necessary.

Elderly population

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

Paediatric population:

Betahistine tablets are not recommended for use in children and adolescents below age 18 due to lack of data on safety and efficacy.

Method of administration

Take the tablets preferably with meals or after meals with a glass of water.

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.

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 monoamino-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.

Pregnancy:

There are no adequate data from the use of betahistine in pregnant women. Animal studies, do not indicate direct or indirect harmful effects with respect to reproductive toxicity at clinically relevant therapeutic exposure. As a precautionary measure, it is preferable to avoid the use of betahistine during pregnancy.

Lactation:

It is not known whether betahistine is excreted in human milk. Betahistine is excreted in rat milk. Effects seen post-partum in animal studies were limited to very high doses. The importance of the drug to the mother should be weighed against the benefits of nursing and the potential risks for the child.

Fertility:

Animal studies did not show effects on fertility in rats.

Betahistine is indicated for vertigo, tinnitus and hearing loss associated with Ménière's syndrome which can negatively affect the ability to drive and use machines. In clinical studies specifically designed to investigate the ability to drive and use machines, betahistine had no or negligible effects.

The following undesirable effects have been experienced with the below indicated frequencies in betahistine-treated patients in placebo-controlled clinical trials and in post-marketing reports: 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); and not known (frequency cannot be estimated from the available data).

Gastrointestinal disorders

Common: nausea and dyspepsia

Nervous System disorders

Common: headache

In addition to those events reported during clinical trials, the following undesirable effects have been reported spontaneously during post-marketing use and in scientific literature. A frequency cannot be estimated from the available data and is therefore classified as “not known”.

Immune System disorders

Not known: Hypersensitivity reactions e.g. anaphylaxis

Gastrointestinal disorders:

Not known: 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.

Skin and subcutaneous tissue disorders

Not known: Cutaneous and subcutaneous hypersensitivity reactions in particular angioneurotic oedema, urticaria, rash, and pruritus.

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.

Pharmacotherapeutic group: 2.7 Central Nervous System. Antiemetic and anti-vertigo

ATC code: N07C A01

The mechanism of action of betahistine is only partly 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 characterized 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.

Absorption:

Orally administered betahistine is readily and almost completely absorbed from all parts of the gastro-intestinal tract. After absorption, the drug is rapidly and almost completely metabolized 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 Cmax 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 metabolized 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.

Repeated dose toxicity studies of six months duration in dogs and 18 months duration in albino rats revealed no clinically relevant harmful effects at dose levels in the range 2.5 to 120 mg. kg^–1. Betahistine is devoid of mutagenic potential and there was no evidence of carcinogenicity in rats. Tests conducted on pregnant rabbits showed no evidence of teratological effects.

Reproduction toxicity

Effects in reproductive toxicity studies were observed only at exposures considered sufficiently in excess of the maximum human exposure indicating little relevance to clinical use.

Cellulose microcrystalline (Avicel PH 101), Mannitol, Povidone, Crospovidone, Citric acid, anhydrous, Methanol, Cellulose microcrystalline (Avicel PH 112), Silica colloidal anhydrous, Talc and Stearic acid.

Not applicable.

Store below 30⁰C.

Blister pack

Betaquil 8, 16 & 24 mg are supplied in 30’s pack (10’s Blister x 3).

Any unused medicinal product or waste material should be disposed of in accordance with local requirements.