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BETAHISTINE DIHYDROCHLORIDE TABLETS 16MG

Active substance(s): BETAHISTINE DIHYDROCHLORIDE / BETAHISTINE DIHYDROCHLORIDE

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SUMMARY OF PRODUCT CHARACTERISTICS

1

NAME OF THE MEDICINAL PRODUCT
Betahistine Dihydrochloride 16mg Tablets

2

QUALITATIVE AND QUANTITATIVE COMPOSITION
Each tablet contains Betahistine dihydrochloride 16 mg
Excipient(s) with known effect: Each tablet contains 100 mg lactose
For a full list of excipients, see section 6.1.

3 PHARMACEUTICAL FORM
Tablets for oral administration
Flat white tablets, with bevelled edge. Markings: R4 on one side scoreline on the
reverse.
The score line is only to facilitate breaking for ease of swallowing and not to divide
into equal doses.

4.1 Therapeutic indications
Betahistine is indicated for the treatment of vertigo, tinnitus and hearing loss
associated with Meniere’s syndrome.

4.2

Posology and method of administration
Posology:
Adults(including the elderly);
Initially 16mg 3 times daily, taken preferably with meals.
Maintenance doses are generally in the range 24-48mg daily.
Paediatric population: not recommended for use in children below 18 years
due to insufficient data on safety and efficacy.

Geriatric population: although there are limited data from clinical studies in

this patient group, extensive post marketing experience suggests that no dose
adjustment is necessary in this patient population.
Renal impairment: there are no specific clinical trials available in this patient
group, but according to post-marketing experience no dose adjustment
appears to be necessary.
Hepatic impairment: there are no specific clinical trials available in this
patient group, but according to post-marketing experience no dose adjustment
appears to be necessary.
Method of Administration:
Swallow the tablet with water
4.3

Contraindications

Betahistine is contraindicated in patients with a phaeochromocytoma and hypersensitivity to
betahistine dihydrochloride or any of the excipients listed in section 6.1.

4.4

Special warnings and precautions for use
Caution is advised in the treatment of patients with a history of peptic
ulcer. Clinical intolerance to betahistine dihydrochloride in bronchial
asthma patients has been shown in a relatively few patients and
therefore caution should be exercised when administering betahistine to
patients with bronchial asthma.
Lactose
Patients with rare hereditary problems of galactose intolerance, the Lapp
lactase deficiency or glucose-galactose malabsorption should not take this
medicine.

4.5

Interaction with other medicinal products and other forms of interaction
No in-vivo interaction studies have been performed. Based on invitro data no in-vivo inhibition on Cytochrome P450 enzymes is
expected.
In vitro data indicate an inhibition of betahistine metabolism by drugs that
inhibit monoamino- oxidase (MAO) including MAO subtype B (e.g.
selegiline). Caution is recommended when using betahistine and MAO
inhibitors (including MAO-B selective) concomitantly.
As betahistine is an analogue of histamine, interaction of betahistine with
antihistamines may in theory affect the efficacy of one of these drugs.

4.6

Fertility, pregnancy and lactation
Pregnancy:
There are no adequate data from the use of betahistine in pregnant women. Animal
studies are insufficient with respect to effects on pregnancy, embryonal/foetal
development, parturition and postnatal development. The potential risk for humans is
unknown. Betahistine should not be used during pregnancy unless clearly necessary.
Lactation:
It is not known whether betahistine is excreted in human milk. There are no animal
studies on the excretion of betahistine in milk. The importance of the drug to the
mother should be weighed against the benefits of nursing and the potential risks for
the child.

4.7

Effects on ability to drive and use machines
Vertigo, tinnitus and hearing loss associated with Meniere’s syndrome can
negatively affect the ability to drive and use machines. In clinical studies
specifically designed to investigate the ability to drive and use machines
betahistine had no or negligible effects.

4.8

Undesirable effects
The following undesirable effects have been experienced with the below indicated
frequencies in betahistine-treated patients in placebo-controlled clinical trials [very
common (≥1/10); common (≥1/100 to <1/10); uncommon (≥1/1,000 to<1/100); rare
(≥1/10,000 to <1/1,000); very rare (<1/10,000)].
Gastrointestinal disorders:
Common: nausea and dyspepsia
Nervous System disorders:
Common: headache
In addition to those events reported during clinical trials, the following undesirable
effects have been reported spontaneously during post-marketing use and in scientific
literature. A frequency cannot be estimated from the available data and is therefore
classified as “not known”.
Immune System disorders:
Hypersensitivity reactions, e.g. anaphylaxis have been reported.
Gastrointestinal disorders:
Mild gastric complaints (e.g. vomiting, gastrointestinal pain, abdominal distension
and bloating) have been observed. These can normally be dealt with by taking the
dose during meals or by lowering the dose.
Skin and subcutaneous tissue disorders:

Cutaneous and subcutaneous hypersensitivity reactions have been reported, in
particular angioneurotic oedema, urticaria, rash, and pruritus.
Reporting of suspected adverse reactions
Reporting suspected adverse reactions after authorisation of the medicinal product 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
via the national reporting system via Yellow Card Scheme at
www.mhra.gov.uk/yellowcard.

4.9

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

5.1.

Pharmacodynamic properties
Pharmacotherapeutic group :Antivertigo preparation. ATC Code: NO7CA01
The mechanism of action of betahistine is only partly understood. There are
several plausible hypotheses that are supported by animal studies and human
data:
• Betahistine affects the histaminergic system:
Betahistine acts both as a partial histamine H1-receptor agonist and histamine
H3-receptor antagonist also in neuronal tissue, and has negligible H2-receptor
activity. Betahistine increases histamine turnover and release by blocking
presynaptic H3-receptors and inducing H3-receptor downregulation.
• Betahistine may increase blood flow to the cochlear region as well as to the
whole brain:
Pharmacological testing in animals has shown that the blood circulation in the
striae vascularis of the inner ear improves, probably by means of a relaxation
of the precapillary sphincters of the microcirculation of the inner ear.
Betahistine was also shown to increase cerebral blood flow in humans.
• Betahistine facilitates vestibular compensation:
Betahistine accelerates the vestibular recovery after unilateral neurectomy in
animals, by promoting and facilitating central vestibular compensation; this
effect characterized by an up-regulation of histamine turnover and release, is
mediated via the H3 Receptor antagonism. In human subjects, recovery time
after vestibular neurectomy was also reduced when treated with betahistine.
• Betahistine alters neuronal firing in the vestibular nuclei:

Betahistine was also found to have a dose dependent inhibiting effect on spike
generation of neurons in lateral and medial vestibular nuclei.
The pharmacodynamic properties as demonstrated in animals may contribute
to the therapeutic benefit of betahistine in the vestibular system.
The efficacy of betahistine was shown in studies in patients with vestibular
vertigo and with Meniere’s disease as was demonstrated by improvements in
severity and frequency of vertigo attacks

5.2

Pharmacokinetic properties
Absorption:
Orally administered betahistine is readily and almost completely absorbed
from all parts of the gastro-intestinal tract. After absorption, the drug is rapidly
and almost completely metabolized into 2-pyridylacetic acid. Plasma levels of
betahistine are very low. Pharmacokinetic analyses are therefore based on 2PAA measurements in plasma and urine.
Under fed conditions Cmax is lower compared to fasted conditions. However,
total absorption of betahistine is similar under both conditions, indicating that
food intake only slows down 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 rapidly and almost completely metabolized
into 2-PAA (which has no pharmacological activity).
After oral administration of betahistine the plasma (and urinary) concentration
of 2-PAA reaches its maximum 1 hour after intake and declines with a halflife of about 3.5 hours.
Excretion:
2-PAA is readily excreted in the urine. In the dose range between 8 and 48 mg,
about 85% of the original dose is recovered in the urine. Renal or faecal
excretion of betahistine itself is of minor importance.
Linearity:
Recovery rates are constant over the oral dose range of 8 – 48 mg indicating
that the pharmacokinetics of betahistine are linear, and suggesting that the
involved metabolic pathway is not saturated.

5.3

Preclinical safety data
Repeat oral dose toxicity studies in dogs and rats for 6 and 18 months
respectively revealed no clinically relevant adverse effects. Betahistine was
not mutagenic in conventional in vitro and in vivo studies of genotoxicity.
Histopathological examination in the 18 months chronic toxicity study
indicated no carcinogenic effects. However, specific carcinogenicity studies
were not performed with Betahistine. Limited studies of reproductive toxicity
in rats and rabbits showed no teratogenic effects.

6.1

LIST OF EXCIPIENTS
Lactose
Citric acid
Microcrystalline cellulose
Maize starch
Crospovidone
Povidone K25
Sodium stearyl fumarate

6.2

Incompatibilities
Not applicable.

6.3

Shelf life
2 years

6.4

Special precautions for storage
Do not store above 30ºC.

6.5

Nature and contents of container
Betahistine Dihydrochloride 16mg Tablets are packed in blister packs
contained in a cardboard carton.
Pack sizes: 84, 100 and 120 Tablets
Not all pack sizes may be marketed.

6.6

Special precautions for disposal
Not applicable.

7

MARKETING AUTHORISATION HOLDER
RI Pharma Ltd,
First Floor, 6 St. John's Court,
Upper Fforest Way,
Swansea Enterprise Park,
Swansea,
Wales
SA6 8QQ

8

MARKETING AUTHORISATION NUMBER(S)
PL 34976/0004

9

DATE OF FIRST AUTHORISATION/RENEWAL OF THE
AUTHORISATION
23/03/2006

10

DATE OF REVISION OF THE TEXT
09/08/2016

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Source: Medicines and Healthcare Products Regulatory Agency

Disclaimer: Every effort has been made to ensure that the information provided here is accurate, up-to-date and complete, but no guarantee is made to that effect. Drug information contained herein may be time sensitive. This information has been compiled for use by healthcare practitioners and consumers in the United States. The absence of a warning for a given drug or combination thereof in no way should be construed to indicate that the drug or combination is safe, effective or appropriate for any given patient. If you have questions about the substances you are taking, check with your doctor, nurse or pharmacist.

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