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 recommended starting dose is 24 mg betahistine.
If this dosage is insufficient, the maximum daily dose can be increased to 48 mg betahistine.
If the maximum daily dose of 48 mg is indicated, adults should take one 24 mg tablet twice per day (in
the morning and in the evening).
The dosage should be individually adapted according to the response.
Paediatric population
The use of Betaserc 24 is not recommended in children up to the age of 18 years, because of a lack of
sufficient data on safety and efficacy.
Older population
Although there is limited data available from clinical trials related to this patient group, extensive
post-marketing experience suggests that no dose adjustment is necessary in this patient population.

Renal impairment
There is no specific data from clinical trials available for this patient group, but post-marketing
experience suggests that no dose adjustment is necessary.

Hepatic impairment

There is no specific data from clinical trials available for this patient group, but post-marketing
experience suggests that no dose adjustment is necessary.
Method of administration
Preferably to be swallowed with water during meals.

Treatment duration
Improvement may sometimes only be observed after a few weeks of treatment. The best results are
sometimes obtained after a number of months. There are indications that treatment from the beginning
of the condition prevents the progression of the illness and/or hearing loss at a later phase of the
illness.

Patients with bronchial asthma and a history of peptic ulcer must be carefully monitored during
treatment.

No in vivo interaction studies have been performed. Based on in vitro data, no in vivo inhibition
of cytochrome P450 enzymes is to be expected.
In vitro data indicate inhibition of betahistine metabolism by medicines that inhibit monoamineoxidase
(MAO), including MAO subtype B (e.g. selegiline). Caution is recommended with
concomitant use of betahistine and MAO inhibitors (including selective MAO-B inhibitors).
As betahistine is an analogue of histamine, interaction of betahistine with antihistamines may in theory
affect the efficacy of one of these drugs.

Pregnancy
There are no adequate data from the use of betahistine in pregnant women. There are insufficient data
from animal studies regarding effects on pregnancy, embryonal/fetal development, parturition and
postnatal development. The potential risk for humans is not known. Betahistine should not be used
during pregnancy unless strictly necessary.
Breast-feeding
It is not known whether betahistine is excreted in human milk. No studies have been performed on the
excretion of betahistine in animal milk. The importance of the medicinal product being taken by the
mother must be weighed up against the benefits of breast-feeding and the potential risk for the infant.

Betahistine is indicated for Ménière's syndrome, which is defined by the following triad of core
symptoms: vertigo, loss of hearing and tinnitus. The disease can negatively affect the ability to drive
and use machines. In clinical studies specially devised to investigate the influence of betahistine on the
ability to drive and use machines, no negative effects or negligible negative effects were observed.

The following undesirable effects have been observed with the frequencies indicated below in patients
treated with betahistine, in placebo-controlled clinical trials: very common (≥1/10); common (≥l/100,
< 1/10); uncommon (≥1/1,000, < 1/100); rare (≥1/10,000, <l/1,000); very rare (<l/10,000).
Gastrointestinal disorders:
Common: nausea and dyspepsia.
Nervous system disorders
Common: headache.

In addition to these undesirable effects, which were reported during clinical trials, the following
undesirable effects have been spontaneously reported during post-marketing use and in scientific
literature. Frequency cannot be estimated from the available data and these undesirable effects are
therefore classified as "not known".
Immune system disorders:
Hypersensitivity reactions, e.g. anaphylaxis
Gastrointestinal disorders:
Mild gastric complaints (e.g. vomiting, gastrointestinal pain, abdominal distension and bloating).
These can usually be prevented by taking the dose during meals or reducing the dose.
Skin and subcutaneous tissue disorders:
Cutaneous and subcutaneous hypersensitivity reactions, in particular angioneurotic oedema, urticaria,
rash, and pruritus.

Reporting of suspected adverse reactions
Reporting of suspected adverse reactions post-marketing authorisation is important. It allows
continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are
asked to report any suspected adverse reactions.

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

A few cases of overdose have been reported. Some patients have experienced mild to moderate
symptoms on doses of up to 640 mg (e.g. nausea, somnolence, abdominal pain).
More serious complications (e.g. convulsions, pulmonary or cardiac complications) have been
observed following intentional overdose of betahistine, especially in combination with other
overdosed medications. Treatment of overdose should include standard supportive measures.

Pharmacotherapeutic group: antivertigo preparations, ATC-code: N07CA01

Mechanism of action
The mechanism of action of betahistine is only partially known. There are various plausible
hypotheses which are supported by animal studies and by human data:

• Betahistine influences the histaminergic system:
Betahistine works both as a partial histamine H1-receptor agonist and as a histamine H3-receptor
antagonist, also in neuronal tissue, and has negligible H2-receptor activity. Betahistine increases
the synthesis and release of histamine by blocking the presynaptic H3-receptors and inducing
H3-receptor downregulation.

• Betahistine can cause an increase in the blood flow to both the cochlear environment and to the
brain as a whole:
Pharmacological studies in animals have shown that the blood flow in the stria vascularis of the
inner ear improves, probably due to a relaxant effect on the precapillary sphincters of the
microcirculation in the inner ear. It has also been shown that betahistine increases cerebral
blood flow in humans.
• Betahistine facilitates vestibular compensation:
Betahistine accelerates vestibular healing after unilateral neurectomy in animals by stimulating
and facilitating central vestibular compensation; this effect, which is characterised by an
increase in the synthesis and release of histamine, is mediated via the H3-receptor antagonism.
The recovery period after vestibular neurectomy has also been reduced after treatment with
betahistine in humans.
• Betahistine alters the neuron firing in the vestibular nuclei:
It has also been discovered that betahistine has a dose-dependent inhibiting effect on the
occurrence of neuron peaks in the lateral and medial vestibular nuclei.

Pharmacodynamic effects
The pharmacodynamic properties, as demonstrated in animals, may contribute to the
therapeutic benefit of betahistine in the vestibular system.
Clinical efficacy and safety
The efficacy of betahistine has been demonstrated in studies of patients with vestibular vertigo and
with Ménière's disease, as evidenced by improvements in the severity and frequency of vertigo attacks.

Absorption
Orally administered betahistine is readily and fully absorbed from all parts of the gastro-intestinal
tract. After absorption, it is quickly and almost completely 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.
The Cmax is lower during food consumption than it is during fasting. However, the total absorption of
betahistine is comparable in both circumstances, which indicates that food only slows the absorption
of betahistine.

Distribution
The percentage of betahistine that is bound by blood plasma proteins is less than 5%.
Biotransformation
After absorption, betahistine is quickly and almost completely metabolised into 2-PAA (which has no
pharmacological activity).
After oral administration of betahistine, the plasma (and urine) concentrations of 2-PAA reach their
maximum levels 1 hour after administration and decline with a half-life of approximately 3.5 hours.

Elimination
2 PAA is readily excreted in the urine. In the dose range between 8 and 48 mg, about 85% of the
original dose is excreted in the urine. There is minor renal or faecal excretion of betahistine itself.
Linearity/non-linearity
Recovery rates over the oral dosage range of 8-48 mg are constant, which indicates that the
pharmacokinetics of betahistine are linear and suggests that the metabolic trajectory involved is not
saturated.

Chronic toxicity
Undesirable effects which affect the central nervous system have been observed in dogs and baboons
after intravenous doses of 120 mg/kg and above.
Studies of the chronic oral toxicity of betahistine dihydrochloride were performed in rats for a period
of 18 months and in dogs for a period of 6 months.
Dosages of 500 mg/kg in rats and 25 mg/kg in dogs were well tolerated without changes in the
clinical-chemical and haematological parameters. There were no histological findings related to these
dosages. After increasing the dosage to 300 mg/kg, the dogs began to vomit. In an experimental study
of betahistine in which rats were treated for a period of 6 months with 39 mg/kg and above, there were
reports in the literature of hyperaemia in some tissues. The data presented in this publication are
limited. Therefore the impact of the findings of this study are not clear.
Mutagenic and carcinogenic potential
Betahistine has no mutagenic potential.

No special carcinogenicity studies have been performed on betahistine dihydrochloride. In the 18-
month-long chronic toxicity studies in rats, however, the histopathological investigation showed no
evidence whatsoever of tumours, neoplasms or hyperplasia. Therefore, in this limited 18-month study,
betahistine dihydrochloride showed no evidence whatsoever of carcinogenic potential at dosages of up
to 500 mg/kg.
Reproductive toxicity
There are limited data available about the effect of betahistine on reproduction. In a one-generation
study in rats, an oral dose of 250 mg/kg/day of betahistine had no detrimental effects on male or
female fertility, on fetal implantation, on parturition, or on pup viability during lactation. No
abnormalities were found in lactating rats. In pregnant rabbits that received oral doses of 10 or 100
mg/kg betahistine, no detrimental effects were observed in implantation, viability or weight of the
fetuses, and no abnormalities of the fetal skeleton or soft tissue were observed. From these studies, it
can be concluded that betahistine has no detectable effects on relevant reproduction parameters in rats
and in rabbits in the studies described. Betahistine is not teratogenic. However, since the studies were
of an investigatory nature, such risks cannot be completely ruled out.

Betaserc 24 tablets contain Microcrystalline cellulose, mannitol (E421), citric acid monohydrate,
colloidal anhydrous silica and talc.

Not applicable.

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

Betaserc 24 tablets come in packs of 20, 50, 60 and 100 tablets, packaged in PVC/PVDC blister packs
containing 10 to 20 tablets with a grey aluminium cover foil.
Not all pack sizes may be marketed.

Any unused product or waste material should be disposed of in accordance with local requirements.