Betahistine dihydrochloride or betahistine mesilate: two sides of the same coin or two different coins

Avijit Hazra, Niteeka Maroo


The antivertigo drug betahistine exerts a histamine modulatory action in the vestibular system and the brain. It is marketed both as the dihydrochloride and the mesilate salt in India. We conducted a published literature based systematic review to ascertain differences, in any, between the salt and ester forms of the drug. Search of the Medline database was supplemented by searching through references in full text papers and retrieving summary of product characteristic literature. Although the weight of published evidence is greater for betahistine dihydrochloride, in the absence of head-to-head studies comparing the efficacy of the two formulations in Ménière's disease and other vertigo disorders of vestibular origin, it is not possible to conclude that there are definite differences in this regard. However, potentially relevant differences exist to suggest that the two forms are not interchangeable for the treatment of vestibular dysfunction. Molecular weight comparison indicates that the pill burden would be higher for betahistine mesilate for delivering equivalent doses. There could be ethnically influenced differences in pharmacokinetic behavior. There are concerns of potential long-term DNA toxicity due to mesilate ester contaminants during production of betahistine mesilate, which is not there for the hydrochloride form. Detailed post-marketing surveillance data exists only for the dihydrochloride salt. Otorhinolaryngologists and other physicians seeking to optimize treatment with betahistine should be aware of these differences.


Betahistine dihydrochloride, Betahistine mesilate, Ménière's disease, Vertigo, Vestibular dysfunction

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Strupp M, Brandt T. Peripheral vestibular disorders. Curr Opin Neurol. 2013;26:81-9.

Mira E. Betahistine in the treatment of vertigo. History and clinical implications of recent pharmacological researches. Acta Otorhinolaryngol Ital. 2001;21(3,66):1-7.

Popova NF, Chugunova MA, Kunel'skaia NL, Shagaev AS, Boĭko AN, Gusev EI. Betahistine in the treatment of vestibular and coordination disturbances in multiple sclerosis [Article in Russian]. Zh Nevrol Psikhiatr Im S S Korsakova. 2011;111:77-81.

Matsnev EI, Sigaleva EE. Efficacy of histaminergic drugs in experimental motion sickness. J Vestib Res. 2007;17:313-21.

SERC®-16. Summary of Product Characteristics uploaded to UK electronic Medicines Compendium (eMC) [Document on the internet]. BGP Products Limited, UK. 2015 April 14 [cited 2016 May 28]. Available at:

MERISLON® Summary of Product Characteristics [Document on the internet]. Eisai Co., Japan. 2009 [cited 2016 May 28]. Available at:

Bertlich M, Ihler F, Sharaf K, Weiss BG, Strupp M, Canis M. Betahistine metabolites, aminoethylpyridine, and hydroxyethylpyridine increase cochlear blood flow in guinea pigs in vivo. Int J Audiol. 2014;53:753-9.

Tighilet B, Trottier S, Mourre C, Chotard C, Lacour M. Betahistine dihydrochloride interaction with the histaminergic system in the cat: neurochemical and molecular mechanisms. Eur J Pharmacol. 2002;446:63-73.

Tighilet B, Trottier S, Lacour M. Dose- and duration-dependent effects of betahistine dihydrochloride treatment on histamine turnover in the cat. Eur J Pharmacol. 2005;523:54-63.

Gbahou F, Davenas E, Morisset S, Arrang JM. Effects of betahistine at histamine H3 receptors: mixed inverse agonism/agonism in vitro and partial inverse agonism in vivo. J Pharmacol Exp Ther. 2010;334:945-54.

Desmadryl G, Gaboyard-Niay S, Brugeaud A, Travo C, Broussy A, Saleur A, et al. Histamine H4 receptor antagonists as potent modulators of mammalian vestibular primary neuron excitability. Br J Pharmacol. 2012;167:905-16.

Lacour M. Betahistine treatment in managing vertigo and improving vestibular compensation: clarification. J Vestib Res. 2013;23:139-51.

Strupp M, Dieterich M, Brandt T. The treatment and natural course of peripheral and central vertigo. Dtsch Arztebl Int. 2013;110:505-15.

Scholtz AW, Steindl R, Burchardi N, Bognar-Steinberg I, Baumann W. Comparison of the therapeutic efficacy of a fixed low-dose combination of cinnarizine and dimenhydrinate with betahistine in vestibular neuritis: a randomized, double-blind, non-inferiority study. Clin Drug Investig. 2012;32:387-99.

Strupp M, Hupert D, Frenzel C, Wagner J, Hahn A, Jahn K, et al. Long-term prophylactic treatment of attacks of vertigo in Ménière’s disease - comparison of a high with a low dosage of betahistine in an open trial. Acta Otolaryngol. 2008;128:520-4.

Sokolova L, Hoerr R, Mishchenko T. Treatment of vertigo: a randomized, double-blind trial comparing efficacy and safety of Ginkgo biloba extract EGb 761 and betahistine. Int J Otolaryngol. 2014:682439.

Redon C, Lopez C, Bernard-Demanze L, Dumitrescu M, Magnan J, Lacour M, et al. Betahistine treatment improves the recovery of static symptoms in patients with unilateral vestibular loss. J Clin Pharmacol. 2011;51:538-48.

Barak N. Betahistine: what's new on the agenda? Expert Opin Investig Drugs. 2008;17:795-804.

Ali AH, Yanoff LB, Stern EA, Akomeah A, Courville A, Kozlosky M, et al. Acute effects of betahistine hydrochloride on food intake and appetite in obese women: a randomized, placebo-controlled trial. Am J Clin Nutr. 2010;92:1290-7.

Lian J, Huang XF, Pai N, Deng C. Betahistine ameliorates olanzapine-induced weight gain through modulation of histaminergic, NPY and AMPK pathways. Psychoneuroendocrinology. 2014;48:77-86.

Poyurovsky M, Fuchs C, Pashinian A, Levi A, Weizman R, Weizman A. Reducing antipsychotic-induced weight gain in schizophrenia: a double-blind placebo-controlled study of reboxetine-betahistine combination. Psychopharmacology (Berl). 2013;226:615-22.

Snodin DJ. Residues of genotoxic alkyl mesilates in mesilate salt drug substances: real or imaginary problems? Regul Toxicol Pharmacol. 2006;45:79-90.

European Medicines Agency Inspections document EMEA/44714/2008. European Medicines Agency, London. 2008 January 24 [cited 2012 Jan 20]. Available at:

Tomar MS, Patni A, Kumar S, Thudi NR, Dubey SK, Khuroo AH, et al. Pharmacokinetics of 2-pyridyl acetic acid, a major betahistine metabolite in healthy Indian volunteers. Der Pharmacia Lettre. 2009;1:52-9.

Chen XY, Zhong DF, Duan JL, Yan BX. LC-MS-MS analysis of 2-pyridylacetic acid, a major metabolite of betahistine: application to a pharmacokinetic study in healthy volunteers. Xenobiotica. 2003;33:1261-71.

Della Pepa C, Guidetti G, Eandi M. Betahistine in the treatment of vertiginous syndromes: a meta-analysis. Acta Otorhinolaryngol Ital. 2006;26:208-15.

Nauta JJ. Meta-analysis of clinical studies with betahistine in Ménière's disease and vestibular vertigo. Eur Arch Otorhinolaryngol. 2014;271:887-97.

Cavaliere M, Mottola G, Iemma M. Benign paroxysmal positional vertigo: a study of two manoeuvres with and without betahistine. Acta Otorhinolaryngol Ital. 2005;25:107-12.

Kaźmierczak H, Pawlak-Osińska K, Kaźmierczak W. Betahistine in vertebrobasilar insufficiency. Int Tinnitus J. 2004;10:191-3.

Naguib MB, Madian YT. Betahistine dihydrochloride with and without early vestibular rehabilitation for the management of patients with balance disorders following head trauma: a preliminary randomized clinical trial. J Chiropr Med. 2014;13:14-20.

Mukhopadhyay S, Niyogi M, Ray R, Mukhopadhyay BS, Dutta M, Mukherjee M. Betahistine as an add-on: The magic bullet for postoperative nausea, vomiting and dizziness after middle ear surgery? J Anaesthesiol Clin Pharmacol. 2013;29:205-10.

Albera R, Ciuffolotti R, Di Cicco M, De Benedittis G, Grazioli I, Melzi G, et al. Double-blind, randomized, multicenter study comparing the effect of betahistine and flunarizine on the dizziness handicap in patients with recurrent vestibular vertigo. Acta Otolaryngol. 2003;123:588-93.

Bodla R, Thota P, Sarabu A, Mohantha GP, Shanmugam R. Comparison of efficacy and tolerability of cinnarizine with betahistine in the treatment of otogenic vertigo. Int J Pharmaceut Res. 2011;3:36-40.

Monzani D, Barillari MR, Ciufelli AM, Aggazzotti CE, Neri V, Presutti L, et al. Effect of a fixed combination of nimodipine and betahistine versus betahistine as monotherapy in the long-term treatment of Ménière's disease: a 10-year experience. Acta Otorhinolaryngol Ital. 2012;32:393-403.

Gananca MM, Caovilla HH, Gananca FF. Comparable efficacy and tolerability between twice daily and three times daily betahistine for Ménière's disease. Acta Oto-Laryngologica. 2009;129:487-92.

Pialoux P. Study of a programmed release preparation of betahistine mesilate in the treatment of Ménière's disease. Ann Otolaryngol Chir Cervicofac. 1981;98:483-6.

Ohsaki K, Ueno M, Zheng HX, Wang QC, Nishizaki K, Nobuto Y, et al. Evaluation of tinnitus patients by peroral multi-drug treatment. Auris Nasus Larynx. 1998;25:149-54.

Ma FR, Xin Y, Zhao YM, Lü JQ. Efficacy of Betahistine Mesilate combined with Flunarizine Hydrochloride for treating tinnitus. Chinese Journal of Otorhinolaryngology Head and Neck Surgery. 2006 Apr;41(4):269-73.

Yi C, Wenping X, Hui X, Xin H, Xiue L, Jun Z, et al. Efficacy and acceptability of oxcarbazepine vs. carbamazepine with betahistine mesilate tablets in treating vestibular paroxysmia: a retrospective review. Postgrad Med. 2016;128:492-5.

Jeck-Thole S, Wagner W. Betahistine: a retrospective synopsis of safety data. Drug Saf. 2006;29:1049-59.

Benecke H, P'rez-Garrigues H, bin Sidek D, Uloziene I, Sondag E, Theeuwes A. Effects of betahistine on patient-reported outcomes in routine practice in patients with vestibular vertigo and appraisal of tolerability: experience in the OSVaLD study. Int J Tinnitus. 2010 Jun 1;16(1):14-24.

Betts T, Harris D, Gadd E. The effects of two anti-vertigo drugs (betahistine and prochlorperazine) on driving skills. Br J Clin Pharmacol. 1991;32:455-8.

Schneider D, Kiessling B, Wieczorek M, Bognar-Steinberg I, Schneider L, Claussen CF. Influence of 3 antivertiginous medications on the vigilance of healthy volunteers. Int J Clin Pharmacol Ther. 2003;41:171-81.