BetaPax 8

Indications

• Management of vertigo associated with Ménière's disease
• Treatment of balance disorders related to vestibular dysfunction

Dosage

Children: Refer to the BNF for Children for appropriate dosing recommendations in paediatric patients.

Adults: Refer to the BNF for specific dosage guidelines based on the clinical scenario.

Mechanism of action

Betahistine primarily functions as a histamine H1-receptor agonist and a partial H3-receptor antagonist. By stimulating H1 receptors, it induces a vasodilatory effect that increases the permeability of blood vessels in the inner ear, which reduces endolymphatic pressure. This mechanism is crucial in preventing labyrinthine rupture, a condition that can lead to hearing loss in patients with Ménière's disease. Additionally, the partial antagonism of H3 receptors helps to prolong the stimulation of H1 receptors, thereby enhancing its therapeutic effects.

Pharmacodynamics

Betahistine's pharmacodynamic profile involves its action on histamine receptors, particularly in the vestibular system. By alleviating vertigo symptoms associated with Ménière's disease through vasodilation and reduced endolymphatic pressure, it provides significant symptomatic relief during episodes of vertigo. The drug's efficacy in improving blood flow in the inner ear supports its role in managing the balance and auditory dysfunctions linked with vestibular disorders.

Pharmacokinetics

Betahistine is rapidly absorbed after oral administration, with peak plasma concentrations occurring approximately 1 to 2 hours post-dose. It undergoes extensive first-pass metabolism, primarily converting into its active metabolite, 2-pyridyl acetic acid. The drug has a relatively short half-life, necessitating multiple daily doses for optimal efficacy. Betahistine is primarily excreted in the urine, with less than 1% of the dose appearing unchanged. This pharmacokinetic profile highlights the importance of adherence to dosing schedules to maintain therapeutic levels.

Contra-indications

• Pheochromocytoma
• History of hypersensitivity to betahistine or any excipients
• Severe asthma

Adverse effects

• Headache
• Nausea
• Vomiting
• Dyspepsia
• Abdominal pain
• Diarrhoea
• Skin rashes

Interactions

• May enhance the effects of antihistamines
• Caution with other vasodilators
• May interact with monoamine oxidase inhibitors (MAOIs)

Precautions

• Use with caution in patients with peptic ulcer disease
• Monitor for hypersensitivity reactions
• Consider renal impairment when dosing

Pregnancy

Limited data on the use of betahistine in pregnancy. Use only if the potential benefit justifies the potential risk to the fetus.

Breast-feeding

Limited data available. Caution is advised; consult a healthcare professional before use.

Storage

Store below 25°C in a dry place, protect from light. Keep out of reach of children.

Formulations

• Betahistine 8 mg tablets
• Betahistine 16 mg tablets
• Betahistine 24 mg tablets

Mechanism of action

OBE101 is a H1 receptor agonist and partial H3 receptor antagonist. Because inhibition of H1 receptors increases feeding, agonism of H1 receptors by OBE101 should reduce feeding. By also partially antagonizing H3, OBE101 impedes a negative feedback loop that essentially prolongs stimulation of the H1 receptors. Vertigo is a disturbing sensation of movement caused by dysfunction of the labyrinth (inner ear), vestibular nerve, cerebellum, brainstem, or Central Nervous System (CNS). Vestibular forms of vertigo are often accompanied by auditory dysfunctions such as hyperacusis, hearing loss, and tinnitus. In most cases, adaptive mechanisms of the CNS lead to functional recovery after episodes of vertigo, however, syndromes such as Ménière's disease tend to cause the recurrence of vertigo symptoms. This significantly impacts the quality of life and the ability to carry out daily activities. **H1-receptor activity** The mechanism of action of betahistine is multifactorial. Ménière's disease is thought to result from a disruption of endolymphatic fluid homeostasis in the ear. Betahistine mainly acts as a histamine H1-receptor agonist. The stimulation of H1-receptors in the inner ear causes a vasodilatory effect leading to increased permeability of blood vessels and a reduction in endolymphatic pressure; this action prevents the rupture of the labyrinth, which can contribute to the hearing loss associated with Ménière's disease. Betahistine is also purported to act by reducing the asymmetrical functioning of sensory vestibular organs and increasing vestibulocochlear blood flow, relieving symptoms of vertigo. **H3-receptor activity** In addition to the above mechanisms, betahistine also acts as a histamine H3-receptor antagonist, increasing the turnover of histamine from postsynaptic histaminergic nerve receptors, subsequently leading to an increase in H1-agonist activity. H3-receptor antagonism elevates levels of neurotransmitters including serotonin in the brainstem, inhibiting the activity of vestibular nuclei, thus restoring proper balance and decreasing vertigo symptoms.

Pharmacodynamics

Through its actions on the histamine receptors, betahistine provides relief from vertigo associated with Ménière's disease.