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).Other symptoms of Betahistine-Nanolek overdose are vomiting, dyspepsia, ataxia and seizures. More serious complications (convulsion, pulmonary or cardiac complications) were observed in cases of intentional overdose of Betahistine-Nanolek especially in combination with other overdosed drugs. No specific antidote. Gastric lavage and symptomatic treatment are recommended within one hour after intake.
Betahistine-Nanolek is contraindicated in patients with phaeochromocytoma. As Betahistine-Nanolek is a synthetic analogue of histamine it may induce the release of catecholamines from the tumor resulting in severe hypertension.
Not applicable.
The following undesirable effects have been experienced with the below indicated frequencies in Betahistine-Nanolek-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).
Gastrointestinal disorders: | |
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 knownâ€. | |
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.
Repeated dose toxicity studies of six months duration in dogs and 18 months duration in albino rats revealed no clinically relevant harmful effects at dose levels in the range 2.5 to 120 mg. kg -1. Betahistine-Nanolek is devoid of mutagenic potential and there was no evidence of carcinogenicity in rats. Tests conducted on pregnant rabbits showed no evidence of teratological effects.
Betahistine-Nanolek is indicated for treatment of Ménière's syndrome, symptoms of which may include vertigo, tinnitus, hearing loss and nausea
Pharmacotherapeutic group: 2.7 Central Nervous System. Antiemetic and anti-vertigo
ATC code: N07C A01
The mechanism of action of Betahistine-Nanolek is only partially understood.
There are several plausible hypotheses that are supported by animal studies and human data:
Betahistine-Nanolek affects the histaminergic system:
Betahistine-Nanolek 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-Nanolek increases histamine turnover and release by blocking presynaptic H3-receptors and inducing H3-receptor downregulation.
Betahistine-Nanolek 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-Nanolek was also shown to increase cerebral blood flow in humans.
Betahistine-Nanolek facilitates vestibular compensation:
Betahistine-Nanolek accelerates the vestibular recovery after unilateral neurectomy in animals, by promoting and facilitating central vestibular compensation; this effect is characterised 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-Nanolek.
Betahistine-Nanolek alters neuronal firing in the vestibular nuclei:
Betahistine-Nanolek 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-Nanolek in the vestibular system.
The efficacy of Betahistine-Nanolek was shown in studies in patients with vestibular vertigo and with Ménière's disease as was demonstrated by improvements in severity and frequency of vertigo attacks.
Absorption
Orally administered Betahistine-Nanolek 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-Nanolek are very low. Pharmacokinetic analyses are therefore based on 2-PAA measurements in plasma and urine.
Under fed conditions Cmax is lower compared to fasted conditions. However, total absorption of Betahistine-Nanolek is similar under both conditions, indicating that food intake only slows down the absorption of Betahistine-Nanolek.
Distribution
The percentage of Betahistine-Nanolek that is bound by blood plasma proteins is less than 5 %.
Biotransformation
After absorption, Betahistine-Nanolek is rapidly and almost completely metabolised into 2-PAA (which has no pharmacological activity).
After oral administration of Betahistine-Nanolek the plasma (and urinary) concentration of 2-PAA reaches its maximum 1 hour after intake and declines with a half-life 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 fecal excretion of Betahistine-Nanolek 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-Nanolek are linear, and suggesting that the involved metabolic pathway is not saturated.
Caution is advised in the treatment of patients with peptic ulcer or a history of peptic ulceration, because of the occasional dyspepsia encountered in patients on Betahistine-Nanolek.
Patients with bronchial asthma should be monitored carefully during the treatment with Betahistine-Nanolek.
Caution is advised in prescribing Betahistine-Nanolek to patients with either urticaria, rashes or allergic rhinitis, because of the possibility of aggravating these symptoms.
Caution is advised in patients with severe hypotension.
Betahistine-Nanolek is indicated for vertigo, tinnitus and hearing loss associated with Ménière's syndrome which 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-Nanolek had no or negligible effects.
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-Nanolek 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.
No special requirements.
