Betahistine Dihydrochloride 8mg Tablets
SUMMARY OF PRODUCT CHARACTERISTICS
1 NAME OF THE MEDICINAL PRODUCT
Betahistine dihydrochloride 8mg tablets.
2 QUALITATIVE AND QUANTITATIVE COMPOSITION
Each tablet contains 8mg of betahistine dihydrochloride.
One Betahistine dihydrochloride 8mg Tablet contains 70mg lactose monohydrate.
For a full list of excipients, see section 6.1.
3 PHARMACEUTICAL FORM
Tablet.
White, circular, flat bevelled-edge uncoated tablets, impressed B8 on one face with the reverse plain.
4 CLINICAL PARTICULARS
4.1 Therapeutic indications
Betahistine tablets are indicated in the treatment of vertigo, tinnitus and hearing loss associated with Meniere's disease.
4.2 Posology and method of administration
Adults:
Initial dosage: 2 tablets, 3 times daily, preferably with food.
Maintenance dose: The dose may be adjusted according to response to a maintenance dose of between 24 and 48mg daily.
Elderly: No adjustment in dosage is necessary.
Paediatric population: Betahistine is not recommended for use in children below 18 years due to insufficient data on safety and efficacy.
For oral use.
Betahistine dihydrochloride tablets should be taken with a glass of water, preferably with food.
4.3 Contraindications
Betahistine is contraindicated in patients with phaeochromocytoma. As betahistine is a synthetic analogue of histamine it may induce the release of catecholamines from the tumour resulting in severe hypertension.
Hypersensitivity to betahistine dihydrochloride or any of the excipients.
4.4 Special warnings and precautions for use
Betahistine tablets should be administered with caution in patients with a history of peptic ulcer.
Clinical intolerance to betahistine has been demonstrated in patients with bronchial asthma, and caution should therefore be exercised in administration of betahistine tablets to patients with bronchial asthma.
Caution should be exercised in prescribing betahistine tablets to patients with either urticaria or rashes.
Caution is advised in patients with severe hypotension.
Betahistine tablets contain 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
There are no proven cases of hazardous interactions.
There is a case report of an interaction with ethanol and a compound containing pyrimethamine with dapsone and another of potentiation of betahistine with salbutamol.
Betahistine is a histamine analogue, concurrent administration of ^antagonist may cause a mutual attenuation of effect of the active agents.
Fertility, pregnancy and lactation
4.6
Animal studies have not revealed teratogenic effects. It is not known to what extent the drug passes the placenta, and there is insufficient evidence on the safety of betahistine in human pregnancy. Betahistine tablets should only be prescribed when, in the opinion of the physician, potential benefit outweighs potential risk.
There is insufficient information on the excretion of betahistine in human milk. Betahistine should not be used during breast-feeding.
4.7 Effects on ability to drive and use machines
Rare reports of drowsiness associated with betahistine have been made. Patients should be advised that if they are affected in this way they should avoid activities requiring concentration, such as driving or operating machinery.
4.8 Undesirable effects
The frequency categories assigned to the adverse reactions below are estimates; as for most reactions suitable data for calculating incidence are not available. In addition the incidence of adverse reactions associated with betahistine dihydrochloride may vary according to the indication.
Data from clinical trials were used to determine the frequency of very common to rare undesirable effects. The frequencies assigned to all other undesirable effects (i.e., those occurring at <1/1000) were mainly determined using post-marketing data, and refer to a reporting rate rather than a true frequency.
The following convention has been used for the classification of frequency:
very common >1/10, common >1/100 and <1/10, uncommon >1/1000 and <1/100, rare >1/10,000 and <1/1000, very rare <1/10,000.
not known (cannot be estimated from the available data)
|
MedDRA system organ class |
Very common |
Rare |
Very rare |
Unknown |
|
Nervous system disorder |
somnolence |
headaches, occasional drowsiness | ||
|
Gastrointestinal disorder |
vomiting, dry mouth, diarrhoea |
gastrointestinal disturbances, nausea, |
|
dyspepsia | ||||
|
Cardiac disorder |
palpitations | |||
|
Skin and subcutaneous tissue disorder |
urticaria |
skin rashes, pruritus | ||
|
General disorder and administrative site conditions |
asthenia | |||
|
Immune system disorder |
hypersensitivity reactions | |||
|
Blood and lymphatic system disorder |
thrombocytopenia | |||
|
Investigations |
increase of transaminases |
4.9 Overdose
The clinical features of overdose include nausea and vomiting, dyspepsia and ataxia, and seizures at higher doses. There is no specific antidote. Gastric lavage may be appropriate soon after oral administration. Patients should be closely observed and given symptomatic treatment.
5 PHARMACOLOGICAL PROPERTIES
5.1 Pharmacodynamic properties
Pharmaco-therapeutic group: Antivertigo properties. ATC code N07C A01.
Betahistine's H1-agonist activity at histamine receptors in peripheral blood vessels has been demonstrated in man by the abrogation of betahistine-induced vasodilation with the histamine antagonist diphenhydramine. Betahistine has minimal effects on gastric acid secretion (an H2-receptor mediated response).
Mechanism of action of betahisitine in Meniere’s syndrome is unclear. The efficacy of betahistine in the treatment of vertigo may be due to its ability to modify the circulation of the inner ear or due to a direct effect on neurons of the vestibular nucleus.
Single oral doses of betahistine of up to 32 mg in normal subjects produced maximal suppression of induced vestibular nystagmus 3 to 4 hours post-dose, with larger doses being more effective in reducing the nystagmus duration.
Pulmonary epithelial permeability in man is increased by betahistine. This is derived from a reduction in the time of clearance from the lung to blood of a radioactive marker. This action is prevented by oral pre-treatment with terfenadine, a known H1-receptor blocker.
Whilst histamine has positive inotropic effects on the heart, betahistine is not known to increase cardiac output and its vasodilator effect may produce a small fall in blood pressure in some patients.
In man, betahistine has little effect on exocrine glands.
5.2 Pharmacokinetic properties
Absorption
Betahistine is completely absorbed after oral administration, and peak plasma concentrations of 14C-labelled betahistine are attained after approximately one hour of oral administration for fasting subjects.
Distribution
Little or no binding occurs with human plasma proteins.
Metabolism & elimination
Elimination of betahistine takes place mainly by metabolism and the metabolites are subsequently eliminated mainly by renal excretion. 85-90% of the radioactivity of an 8 mg dose appears in the urine over 56 hours, with maximum excretion rates reached within 2 hours of administration. After oral administration of betahistine, its plasma levels are very low. Therefore, the assessment of the pharmacokinetics of betahistine is based on the plasma concentration data of the only metabolite 2-pyridylacetic acid. There is no evidence of presystemic metabolism and biliary excretion is not thought to be an important route of elimination for the drug or any of its metabolites, however betahistine is subject to metabolism in the liver.
5.3 Preclinical safety data
The toxicity of betahistine is relatively low as may be inferred from LD50 values in rats, mice and guinea pigs.
Betahistine has no mutagenic potential and toxicity studies have failed to reveal any harmful effects of clinical significance at dose levels ranging between 2.5 and 120mg kg -1 body weight after 6 months in dogs and 18 months in albino rats. There is no evidence of carcinogenicity in the latter animals nor of teratogenic effects in pregnant rabbits.
6 PHARMACEUTICAL PARTICULARS
6.1 List of excipients
Povidone K90
Microcrystalline cellulose Lactose monohydrate Colloidal anhydrous silica Crospovidone Stearic acid
6.2 Incompatibilities
Not applicable
6.3 Shelf life
Thirty-six months
6.4 Special precautions for storage
Do not store above 25°C. Store in the original package.
6.5 Nature and contents of container
PVDC/PVC/Aluminium blister.
Pack sizes: 60, 84,168 *
* Not all pack sizes may be marketed
6.6 Special precautions for disposal
Not applicable.
7 MARKETING AUTHORISATION HOLDER
Actavis UK Limited (Trading style: Actavis)
Whiddon Valley BARNSTAPLE N Devon EX32 8NS
MARKETING AUTHORISATION NUMBER(S)
PL 00142/0501
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DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION
15 June 2001 / 26 November 2008
DATE OF REVISION OF THE TEXT
19/11/2012