Betahistine

Pharmacologic Category

Histamine H1 Agonist; Histamine H3 Antagonist

Dosing: Adult

Ménière disease (to decrease episodes of vertigo): Oral: 8 to 16 mg 3 times daily or 24 mg twice daily; usual dosage range: 24 to 48 mg daily in divided doses. Doses slowly titrated (ie, approximately every 3 months) up to 480 mg daily (off-label dosing) have been reported in a small number of cases with severe, resistant disease (Lezius 2011).

Dosing: Geriatric

Refer to adult dosing. Use with caution due to likelihood of decreased hepatic/renal function.

Dosing: Renal Impairment: Adult

There are no dosage adjustments provided in the manufacturer's labeling (has not been studied); use with caution.

Dosing: Hepatic Impairment: Adult

There are no dosage adjustments provided in the manufacturer's labeling (has not been studied). Betahistine primarily undergoes hepatic metabolism; use with caution.

Use: Labeled Indications

Note: Not approved in the US

Ménière disease: Treatment of Ménière disease (to decrease episodes of vertigo)

Administration: Oral

Administer with or without meals; administer with meals if adverse GI effects occur.

Storage/Stability

Store at 15°C to 30°C (59°F to 86°F). Protect from moisture.

Contraindications

Hypersensitivity to betahistine or any component of the formulation; presence or history of active peptic ulcer disease; pheochromocytoma

Warnings/Precautions

Disease-related concerns:

• Asthma: Use with caution; clinical intolerance has been reported in a few asthmatic patients.

• Cardiovascular disease: Use with caution in patients with cardiovascular disease; post-market cases of ventricular extrasystoles, hypotension, and tachycardia have been reported during use.

• Hepatic impairment: Use with caution; primarily undergoes hepatic metabolism.

• Peptic ulcer: Exacerbation of symptoms has been observed in patients with a history of peptic ulcer; use is contraindicated in the presence or history of peptic ulcer.

Pregnancy Considerations

Adverse events were observed in some animal reproduction studies.

Breast-Feeding Considerations

It is not known if betahistine is present in breast milk. According to the manufacturer, the decision to continue or discontinue breastfeeding during therapy should take into account the risk of infant exposure, the benefits of breastfeeding to the infant, and benefits of treatment to the mother.

Adverse Reactions

1% to 10%:

Central nervous system: Headache (5%)

Gastrointestinal: Nausea (2%), dyspepsia

Frequency not defined:

Central nervous system: Confusion, convulsions, drowsiness (case reports), hallucination, paraesthesia

Cardiovascular: Hypotension (including orthostatic and postural hypotension), tachycardia, ventricular premature contractions (case reports)

Dermatologic: Pruritus, skin rash, Stevens-Johnson syndrome, urticaria

Gastrointestinal: Abdominal distension, abdominal pain, bloating, peptic ulcer (including exacerbation of previous disease), vomiting

Hypersensitivity: Anaphylaxis, angioedema, hypersensitivity reaction

Respiratory: Dyspnea

Allergy and Idiosyncratic Reactions

• Betahistine Allergy

Metabolism/Transport Effects

None known.

Drug Interactions Open Interactions

Antihistamines: May diminish the therapeutic effect of Betahistine. Risk C: Monitor therapy

Beta2-Agonists: Betahistine may diminish the therapeutic effect of Beta2-Agonists. Risk C: Monitor therapy

Monoamine Oxidase Inhibitors: May increase the serum concentration of Betahistine. Risk C: Monitor therapy

Product Availability

Not available in the US

Dosage Forms: Canada

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Tablet, Oral:

Serc: 16 mg, 24 mg

Generic: 8 mg, 16 mg, 24 mg

Anatomic Therapeutic Chemical (ATC) Classification

• N07CA01

Generic Available (US)

Yes

Mechanism of Action

Partial agonist of histamine at H1 receptor and antagonist at H3 receptor; relatively inactive at H2 receptor. Animal studies suggest that betahistine may increase cochlear blood flow and produce excitatory effects on neuronal activity of cortical and subcortical structures via H1-receptor agonism and decrease vestibular sensory input and increase synthesis and release of histamine from the hypothalamus via H3-receptor antagonism (Ihler 2012; Lacour 2007).

Pharmacodynamics/Kinetics

Absorption: Rapid, complete; delayed by food

Tmax: 1 hour to reach peak levels of inactive metabolite

Protein binding: <5%

Metabolism: Rapid and almost complete hepatic metabolism to 2-pyridylacetic acid (inactive metabolite)

Half-life elimination: ~3.5 hours (inactive metabolite)

Excretion: Urine (~91%; primarily as inactive metabolite)

Local Anesthetic/Vasoconstrictor Precautions

No information available to require special precautions

Effects on Dental Treatment

No significant effects or complications reported

Effects on Bleeding

No information available to require special precautions

Index Terms

Betahistine Dihydrochloride; Betahistine HCl

References

Ihler F, Bertlich M, Sharaf K, et al. Betahistine Exerts a Dose-Dependent Effect on Cochlear Stria Vascularis Blood Flow in Guinea Pigs In Vivo. PLoS One. 2012;7(6):e39086.[PubMed 22745706]

Lacour M, van de Heyning PH, Novotny M, et al. Betahistine in the treatment of Ménière’s disease. Neuropsychiatr Dis Treat. 2007;3(4):429-440.[PubMed 19300572]

Lezius F, Adrion C, Mansmann U, et al. High-dosage betahistine dihydrochloride between 288 and 480 mg/day in patients with severe Meniére’s disease: a case series. Eur Arch Otorhinolaryngol. 2011;268(8):1237-1240.[PubMed 21626121]

Serc (betahistine) [product monograph].Etobicoke, Ontario, Canada: BGP Pharma ULC: August 2017.

Last Updated 4/3/20