Source: Υπουργείο Υγείας (CY) Revision Year: 2020 Publisher: Almirall , S.A., General Mitre, 151, 08022 Barcelona, Spain
Pharmacotherapeutic group: Other antihistamines for systemic use
ATC code: RO6AX22
Ebastine causes rapid and prolonged inhibition of the effects induced by histamine, and has a strong affinity for binding to the H1 receptors.
Neither ebastine nor its metabolites cross the blood-brain barrier after oral administration. This characteristic is in accord with the low sedation profile observed in the results of experiments studying the effects of ebastine on the central nervous system.
In vitro and in vivo data demonstrate that ebastine is a potent H1 histamine receptor antagonist with a prolonged and highly selective effect. It has no adverse effects on the CNS or anticholinergic effects.
Studies carried out on histamine-induced wheals have demonstrated a clinically and statistically significant antihistamine effect, initiating after 1 hour and lasting more than 48 hours. After suspending administration of treatment with ebastine for 5 days, the antihistamine effect was apparent for more than 72 hours. This activity was parallel with plasma levels of the main active acid metabolite, carebastine.
Inhibition of the peripheral receptors remained constant after repeated administration, with the absence of tachyphylaxis. These results suggest that a dose of at least 10 mg of ebastine causes rapid, intense and lasting inhibition of the peripheral H1 histamine receptors following a single daily administration.
Sedation was studied via tests consisting of electroencephalogram, cognitive function, visual-motor co-ordination, as well as subjective estimations. No significant increase in sedation was observed at the recommended dose. These results are in accord with those obtained in double-blind clinical trials: the incidence of sedation is comparable between placebo and ebastine.
The cardiac effects of ebastine were studied in clinical trials. No significant cardiac effects were observed in detailed analyses of doses of up to 100 mg per day (five times the recommended daily dose).
Ebastine is rapidly absorbed after oral administration. It undergoes considerable first pass hepatic metabolism, leading to the appearance of its active acid metabolite, carebastine.
After a single oral dose of 10 mg, maximum plasma levels of the metabolite are obtained between 2.6 and 4 hours and reach values of 80 to 100 ng/ml. The half-life of the acid metabolite is between 15 and 19 h, with some 66% of the compound excreted in urine, mainly as conjugated metabolites. After repeated administration of 10 mg once daily, steady state was reached in 3 to 5 days with maximum plasma levels between 130 and 160 ng/ml.
In vitro studies with human hepatic microsomes demonstrate that the enzyme CYP3A4 mediates the metabolism of ebastine to carebastine. Concomitant administration of ebastine and ketoconazole or erythromycin (both are CYP3A4 inhibitors) to healthy volunteers was associated with significantly elevated ebastine and carebastine plasma concentrations, especially with ketoconazole (see 4.5. Interaction with other medicaments and other forms of interaction).
Both ebastine and carebastine show a high affinity for protein binding, >97%.
No statistically significant differences were observed in the pharmacokinetics profile in the elderly when compared to young adults.
Ebastine and carebastine plasma concentrations obtained on the first and fifth days of treatment in patients in studies of mild, moderate or serious renal impairment (daily doses of 20 mg), and in studies of slight, moderate (both with doses of 20 mg/day) or serious (dose of 10 mg/day) hepatic impairment were similar to those reached in healthy volunteers. The pharmacokinetics profile of ebastine and its metabolite does not undergo significant changes in patients with various degrees of hepatic or renal impairment.
The preclinical data evidenced no significant toxic effects based on conventional studies determining pharmacological safety, toxicity of repeated doses, genotoxicity, potential carcinogenicity and reproduction toxicology.
© All content on this website, including data entry, data processing, decision support tools, "RxReasoner" logo and graphics, is the intellectual property of RxReasoner and is protected by copyright laws. Unauthorized reproduction or distribution of any part of this content without explicit written permission from RxReasoner is strictly prohibited. Any third-party content used on this site is acknowledged and utilized under fair use principles.
