Ménière’s Syndrome as defined by the following core symptoms:
• vertigo (with nausea/vomiting)
• hearing loss (hardness of hearing)
• tinnitus (ringing in the ears)
Symptomatic treatment of vestibular vertigo.

Posology
The dosage for adults is 24-48 mg, spread over the day.
8 mg tablet: 1 to 2 tablets 3x daily
16 mg tablet: ½ to 1 tablet 3x daily
The dose may be adjusted in the light of the results. The improvement may be so gradual that this is
only noticeable after a few weeks.
Paediatric patients:
Administration of Betaserc to children is not recommended. No data are known on the efficacy and
safety in children and young adults aged under 18 years.

Elderly patients:
Although there are limited data from clinical trials in this patient group post-marketing experience
suggests that in elderly patients it is not necessary to adjust the dose.
Patients with reduced renal function:
There are no data available from clinical trials, but based on post-marketing experience adjustment of
the dose is not necessary in patients with a reduced renal function.
Patients with reduced hepatic function:
There are no data available from clinical trials, but based on post-marketing experience adjustment of
the dose is not necessary in patients with a reduced hepatic function.

Patients with bronchial asthma and patients with a history of peptic ulcer should be carefully monitored
during treatment.
Caution should be exercised in patients with severe hypotension.

No in vivo trials have been carried out. Based on in vitro data no in vivo inhibition of Cytochrome
P450 enzymes is anticipated.
In vitro data indicate inhibition of the metabolism of betahistine by medicinal products that inhibit
monoamine oxidase (MAO), including MAO subtype B (for example selegiline). Caution should be
exercised with concomitant use of betahistine and MAO inhibitors (including selective MAO-B
inhibitors).
Since betahistine is an analogue of histamines, interaction of betahistine with antihistamines may in
theory influence the efficacy of these products.

Pregnancy
There are insufficient data on the use of betahistine dihydrochloride during pregnancy in humans. In
animal studies no indications were found of harmful effects on the pregnancy, the embryonal and foetal
development, the birth and postnatal development. The potential risk to humans is not known. Betaserc
should not be used during pregnancy unless strictly necessary.
Lactation
It is not known whether betahistine dihydrochloride is excreted in the breast milk. There are no animal
studies on the excretion of betahistine dihydrochloride in milk. A risk for the infant cannot be excluded.

The importance of taking the medicinal product by the mother should be weighed carefully against the
benefits of breastfeeding and the potential risk for the child.

Betahistine is indicated for Ménière’s disease. This disorder may adversely affect the ability to drive
and operate machines. Clinical trials specially designed to investigate the ability to drive and operate
machines showed that betahistine has little or no effect on this.

The following unexpected side effects were found in placebo-controlled clinical trials with the
frequencies indicated below:
The side effects are shown per organ class and with frequency of occurrence. Here:
Very common: more than 1 in 10 patients (>10).
Common: more than 1 in 100 patients and less than 1 in 10 patients (>1/100, <1/10).
Uncommon: more than 1 in 1000 patients and less than 1 in 100 patients (>1/1000, >1/100).
Rare: more than 1 in 10,000 patients and less than 1 in 1000 patients (>1/10,000, <1/1000).
Very rare: less than 1 in 10,000 patients, including isolated cases (<1/10,000).
Disorders of the nervous system:
Common: headache
Gastrointestinal disorders:
Common: nausea, dyspepsia
In addition to these side effects that were reported during clinical trials the following unexpected side
effects were reported spontaneously in scientific literature during post-marketing use. A frequency
cannot be estimated from the available data and these side effects are therefore classified as “unknown”.

Immune system disorders:
Not known: hypersensitivity reactions, including anaphylaxis, have been reported.
Gastrointestinal disorders:
Not known: mild gastric symptoms (such as vomiting, abdominal pain, swollen, distended abdomen).
These can usually be prevented by taking the dose during the meal or by reducing the dose.
Skin and subcutaneous disorders:
Not known: hypersensitive reactions of the skin and dermis, in particular angioneurotic oedema,
urticaria, rash and pruritus.

Reporting suspected adverse effects
It is important after authorisation of the medicinal product to report any suspected adverse effects. In
this way the relationship between benefits and risks of the medicinal product can be constantly
monitored.

To report any side effect(s):
-National Pharmacovigilance Center (NPC)
o Fax: +966-1-205-7662
o Call NPC at +966-11-2038222, Exts: 2317-2356-2353-2354-2334-2340.
o Toll free phone: 8002490000
o E-mail: npc.drug@sfda.gov.sa

A few cases of overdose have been reported. Some patients experienced mild to moderate effects with
doses up to 640 mg (for example nausea, somnolence, abdominal pain). More severe cases (for example
convulsions, lung or heart problems) occurred in case of intentional overdose with betahistine, in
particular in combination with other overdosed medicinal products. Treatment of overdose should
include the standard supporting measures.

Betahistine is classed in the ATC N07CA01.
The action mechanism of betahistine is only partly known. There are different hypotheses from animal
studies and data in humans:

• Betahistine affects the histaminergic system:
In biochemical trials it was found that betahistine has weak H1 receptor agonistic and strong H3
antagonist properties in the central nervous system and autonomous nervous system. The H2
receptor activity was found to be negligible (e.g. stimulation of gastric acid secretion).
Betahistine increases the turnover and release of histamine most probably by blocking
presynaptic H3 receptors and inducing the down-regulation of H3 receptors.
• Betahistine can increase the blood flow to the inner ear:
It has been possible to demonstrate that in pharmacological animal tests betahistine improves the
flow in the stria vascularis of the inner ear, probably due to a relaxing action of the precapillary
sphincters of the microcirculation in the inner ear.
• Betahistine facilitates vestibular compensation:
Betahistine accelerates vestibular healing after unilateral neurectomy in animals by stimulating
and facilitating vestibular compensation; this effect, that is characterised by an increase in
histamine conversion and release, is mediated via the H3 receptor antagonism. Betahistine also
reduces the recovery period after vestibular neurectomy in humans.
• Betahistine changes the discharge of action potentials of the neuron in the vestibular cores:
Betahistine also has a dose-dependent inhibiting effect on the discharge of action potentials of
neurons in the lateral and medial vestibular cores.

• Ménière’s disease is characterised by attacks of dizziness, tinnitus, headache, nausea. In the long
term hearing loss may occur. Clinical studies show that betahistine can prevent an attack and
reduce the severity of the attacks.

Absorption
A betahistine dihydrochloride tablet is quickly and fully absorbed after oral administration from all
parts of the gastrointestinal system. After absorption it is quickly and almost fully metabolised into 2-
pyridylacetic acid (2-PAA). Plasma levels of betahistine are very low. Pharmacokinetic analyses are
therefore based on 2-PAA measurements in plasma and urine. After oral administration of betahistine
the plasma concentration of 2-PAA reaches a maximum after 1 hour.
During food intake the Cmax is lower than during fasting. The total absorption of betahistine is however
comparable under both circumstances, which indicates that food only delays the absorption of
betahistine.

Distribution
The percentage of betahistine that is bound by blood plasma proteins is less than 5%..
Metabolism
After absorption betahistine is quickly and almost fully metabolised into 2-PAA (which has no
pharmacological activity). 2-PAA has a half life period of around 3.5 hours.
Elimination
2-PAA is quickly excreted in the urine. In doses of between 8 and 48 mg, around 85% of the original
dose is excreted in the urine. Excretion via the kidneys or faeces of betahistine itself is of secondary
importance.
Linearity
Recovery rates are constant over the oral dosage range of 8 – 48 mg, which indicates that the
pharmacokinetics of betahistine are linear and suggests that the metabolic path involved is not saturated.

Side effects that affected the central nervous system were only seen in dogs and baboons after
intravenous doses of 120 mg/kg/day, many times higher than relevant to humans. In addition oral doses
of betahistine dihydrochloride, many times higher than human doses, for 18 months in rats and 6
months in dogs showed no adverse effects. Betahistine is not genotoxic.
No carcinogenicity studies have been carried out. Limited studies showed no effects on reproduction in
rats and rabbits.

Microcrystalline cellulose
Mannitol
Citric acid monohydrate

Colloidal anhydrous silica
Talc

No remarks.

Store below 30°C.
Store in the original packaging to protect from light.

8 mg: Betaserc 8
Carton with 100 tablets in PVC/PVDC/Aluminium blister strips.
16 mg: Betaserc 16
Carton with 40 tablets in PVC/PVDC/Aluminium blister strips.

All unused tablets must be destroyed via the pharmacy in accordance with the applicable guidelines for
this.