Betahistine Dihydrochloride 8 Mg Tablets
SUMMARY OF PRODUCT CHARACTERISTICS
1 NAME OF THE MEDICINAL PRODUCT
Betahistine dihydrochloride 8 mg tablets
2 QUALITATIVE AND QUANTITATIVE COMPOSITION
Each tablet contains 8 mg betahistine dihydrochloride.
Each tablet contains 50 mg lactose monohydrate.
For the full list of excipients, see section 6.1
3 PHARMACEUTICAL FORM
Tablet.
White, flat, round tablets with bevelled edges, score line on one side, diameter 6.5 mm.
The score line is only to facilitate breaking for ease of swallowing and not to divide into equal doses.
4 CLINICAL PARTICULARS
4.1 Therapeutic indications
For the treatment of Meniere’s syndrome, symptoms of which may include vertigo, nausea, tinnitus and hearing loss.
4.2
Posology and method of administration
Dosage
Adults:
Initial oral treatment is 8 to 16 mg three times daily, taken preferably with meals.
Maintenance doses are generally in the range 24 - 48 mg daily. Daily dose should not exceed 48 mg. Dosage can be adjusted to suit individual patient needs. Sometimes improvement could be observed only after a couple of weeks of treatment.
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.
Elderly 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 population.
Paediatric population
Betahistine tablets are not recommended for use in children and adolescents below age 18 due to lack of data on safety and efficacy.
Method of administration
Take the tablets preferably with meals or after meals with a glass of water.
4.3 Contraindications
Betahistine is contraindicated in case of:
• Hypersensitivity to the active substance(s) or to any of the excipients listed in section 6.1.
• Phaeochromocytoma. As betahistine is a synthetic analogue of histamine it may induce the release of catecholamines from the tumor resulting in severe hypertension.
4.4 Special warnings and precautions for use
It is recommended to closely monitor patients with a history of peptic ulcers even though studies in healthy subjects showed no elevation of gastric acid secretion by betahistine dihydrochloride.
Caution should be exercised in patients with:
• bronchial asthma.
• urticaria, rashes or allergic rhinitis, because of the possibility of aggravating these symptoms.
• pronounced hypotension.
• concomitant treatment with antihistamines (see section 4.5).
This medicinal product contains lactose. Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose - galactose malabsorption should not take this medicinal product.
4.5 Interaction with other medicinal products and other forms of interaction
There are no studies on the interactions with the following medicinal products also used in the treatment of the disorders mentioned in section 4.1: vasodilators, psychotropic medicinal products, in particular sedatives, tranquillisers and neuroleptics, parasympatholytics, and vitamins.
Betahistine should not be concomitantly administered with antihistamines because animal studies have demonstrated that the effect of both could be diminished.
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 H1 antagonists may cause a mutual attenuation of effect of the active agents.
Note:
If betahistine is to be administered subsequent to the treatment with an antihistamine and this treatment is stopped abruptly, withdrawal symptoms such as sleep disorders and agitation could appear because of the sedative action of antihistamines. Therefore the treatment with the antihistamine should be tapered over approximately 6 days.
No in-vivo interaction studies have been performed. Based on in-vitro data no in-vivo inhibition on Cytochrome P450 enzymes is expected.
In vitro data indicate an inhibition of betahistine metabolism by drugs that inhibit monoaminooxidase (MAO) including MAO subtype B (e.g. selegiline). Caution is recommended when using betahistine and MAO inhibitors (including MAO-B selective) concomitantly.
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 and in post-marketing reports: 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); and not known (frequency cannot be estimated from the available data).
Common: nausea & 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”.
Cardiac disorders:
Not Known: palpitations, tightness of the chest
Immune system disorders:
Not known: hypersensitivity reactions, e.g. anaphylaxis.
Gastrointestinal disorders:
Not known: Mild gastric complaints (e.g. vomiting, gastrointestinal pain, abdominal distension and bloating). These can normally be dealt with by taking the dose during meals or by lowering the dose.
Skin and subcutaneous tissue disorders
Not known: cutaneous and subcutaneous hypersensitivity reactions, in particular
angioneurotic oedema, urticarial, 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 Yellow Card Scheme at: www.mhra.gov.uk/yellowcard.
4.9 Overdose
Symptoms of overdose:
In case of overdose, the following symptoms, analagous to histamine overdose, might occur: headache, redness of the face, vertigo, tachycardia, hypotension, bronchial spasm, oedema, in particular oedema of the mucosa of the upper respiratory tract (Quincke’s oedema).
Treatment of overdose:
There is no specific antidote to betahistine dihydrochloride. In addition to general measures aimed at betahistine elimination (gastric lavage, administration of activated charcoal), treatment should be symptomatic and supportive.
5 PHARMACOLOGICAL PROPERTIES
5.1 Pharmacodynamic properties
Pharmacotherapeutic group: antivertigo preparations
ATC code: N07CA01
Betahistine is a member of the group of beta - 2 pyridylalkylamines. Betahistine is a structural analogue of the endogenous histamine.
The exact biochemical mode of action of betahistine, and its receptor specificity and affinity, has not been elucidated to date.
Betahistine pharmacodynamic studies in animals showed predominantly H1 -receptor agonist activity of betahistine. On the basis of the animal studies, various hypotheses for the mode of action of betahistine on the vestibular function have been postulated.
5.2 Pharmacokinetic properties
There is insufficient data on the pharmacokinetics of betahistine in humans.
Absorption:
Following oral administration betahistine is rapidly and completely absorbed.
Distribution:
No data is available on tissue distribution in man. There is little or no binding to plasma proteins.
Betahistine undergoes rapid and complete biotransformation, probably hepatic, with evidence for the formation of 2 - pyridylacetaldehyde and 2 - (2 -aminoethyl)pyridine.
Elimination:
It is excreted almost quantitatively in urine as the metabolite 2 - pyridylacetic acid within
24 hours. No unchanged betahistine has been detected.
Betahistine is excreted in breast milk at approximately the same level as are found in plasma.
A randomised, single dose bioequivalence study with Betahistine 24 mg tablets on 36 subjects was carried out in 2009. Test and reference were administered orally after a light breakfast. The primary evaluation parameter was the plasma levels of the metabolite 2 - pyridylacetic acid, see Figure 1 following.
The results confirmed bioequivalence of Betahistine 24 mg tablets with the reference product (93.4 % CI), within narrow limits for the area under the curve (AUC, 90 % -110 %) and within conventional limits for maximal plasma concentration (Cmax, 80 % - 125 %).
Table 1: Summary statistics for the primary pharmacokinetic parameters 2 -
pyridylacetic acid following a single dose (1 tablet) of treatment A (Vertimed 24) or treatment B (reference 24 mg tablets)
|
Parameter |
Test A* |
Reference B* |
Test / Reference** |
|
Cmax (ng / ml) |
818.0 (± 352.3 |
875.9 (± 352.7) |
0.93 (0.87 - 0.99) |
|
AUC0 - 00 (ng / ml.h) |
4557.3 (± 2759.0) |
4375.4 (± 2091.1) |
1.00 (0.95 - 1.07) |
|
T1 / 2 (h) |
3.15 (± 0.78) |
3.10 (± 0.78) |
1.02 (0.96 - 1.08) |
* Arithmetic mean (± SD)
5.3 Preclinical safety data
There are no findings from preclinical chronic toxicity studies that suggest any increased risk associated with use in humans. Betahistine has been inadequately investigated for its toxicity in relation to reproduction. No adequate mutagenicity or carcinogenicity studies are available.
6 PHARMACEUTICAL PARTICULARS
6.1 List of excipients
Lactose monohydrate
Maize starch
Cellulose microcrystalline, E 460 Citric acid, anhydrous, E 330 Povidone K 25, E 1201
Crospovidone type A, E 1202
Hydrogenated vegetable oil
6.2 Incompatibilities
Not applicable.
6.3 Shelf life
3 years.
6.4 Special precautions for storage
This medicinal product does not require any special storage conditions.
6.5 Nature and contents of container
Blisters of PVC / PE / PVDC - aluminium.
Packs of 14, 20, 24, 28, 30, 48, 50, 60, 84, 90, 96, and 100 tablets are available. Not all pack sizes may be marketed.
6.6 Special precautions for disposal
Any unused product or waste material should be disposed of in accordance with local requirements.
7 MARKETING AUTHORISATION HOLDER
Morningside Healthcare Ltd 115 Narborough Road Leicester LE3 0PA
8 MARKETING AUTHORISATION NUMBER(S)
PL 20117/0236
9 DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION
29/06/2015
10 DATE OF REVISION OF THE TEXT
29/06/2015