Betahistine

Betahistine is a structural analog of histamine, used as the dihydrochloride or mesilate salt. There is no FDA-approved betahistine product in the US. It is licensed in many other countries, for example as Serc. Lake Hills Pharmacy uses betahistine bulk drug substance in compounded oral capsules.

No FDA-labeled indication or dose exists. Outside the US, betahistine is licensed for vertigo, tinnitus and hearing loss associated with Ménière's disease. Prescribers in the US use compounded betahistine for Ménière's disease and other vestibular disorders.

Evidence is mixed: a Cochrane review rated the available evidence as low quality, and the largest placebo-controlled trial (BEMED, 2016) found no difference in attack frequency compared with placebo. The 2020 AAO-HNS guideline lists betahistine among options a clinician may offer for maintenance therapy.

Betahistine is a weak partial agonist at histamine H1 receptors and a potent antagonist (inverse agonist) at H3 receptors, with negligible H2 activity. H3 blockade increases histamine synthesis and release, which is thought to increase cochlear and vestibular microcirculation, reduce firing in the vestibular nuclei and facilitate central vestibular compensation.

Betahistine is rapidly and almost completely absorbed but undergoes extensive first-pass metabolism, mainly by monoamine oxidase, to the inactive metabolite 2-pyridylacetic acid, so plasma levels of the parent drug are very low. The metabolite peaks about 1 hour after dosing and has a half-life of about 3.5 hours. Elimination is almost entirely urinary within 24 hours. Food lowers peak levels without changing the extent of absorption.

• Hypersensitivity to betahistine or any component.
• Pheochromocytoma.

• Bronchial asthma: monitor patients with asthma during treatment.
• History of peptic ulcer: use with caution, as gastrointestinal effects can occur.
• Not recommended for children and adolescents because data are insufficient.
• Hypersensitivity reactions, including skin reactions and angioedema, require stopping the drug.

• Monoamine oxidase inhibitors, including MAO-B selective agents such as selegiline: inhibit betahistine metabolism and can increase exposure.
• H1 antihistamines: may in theory reduce the effect of betahistine, and betahistine may reduce the effect of antihistamines.

Common: nausea, dyspepsia and headache. Others: vomiting, abdominal pain, bloating and mild gastrointestinal discomfort, often reduced by taking it with food. Hypersensitivity reactions, including anaphylaxis, rash, pruritus, urticaria and angioedema, have been reported.

Data on use in pregnancy are insufficient; avoid unless clearly necessary. Whether betahistine is excreted in human milk is unknown; the prescriber weighs the benefit of breastfeeding against the benefit of therapy.

Frequency and severity of vertigo episodes, hearing and tinnitus as assessed by the prescriber, gastrointestinal tolerability, asthma symptoms in patients with asthma, and signs of hypersensitivity.

• Serc (betahistine dihydrochloride) Summary of Product Characteristics (non-US label).
• Clinical Practice Guideline: Ménière's Disease (2020), American Academy of Otolaryngology–Head and Neck Surgery Foundation.
• Murdin L, Hussain K, Schilder AGM. Betahistine for symptoms of vertigo. Cochrane Database of Systematic Reviews, 2016.
• Martindale: The Complete Drug Reference, betahistine monograph.