Aleva

Each tablet contains: Ebastine BP 10 mg or 20 mg.

Antihistamine.
Pharmacology: Pharmacodynamics: Pre-Clinical: Ebastine has been shown to produce a rapid and long-lasting inhibition of histamine-induced effect and to have a strong affinity towards H₁-receptors. Following oral administration neither Ebastine or its metabolites cross the blood brain barrier. This characteristic is consistent with the low sedative profile seen 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, long-lasting and highly selective histamine H₁-receptor antagonist devoid of untoward CNS actions and anticholinergic effects.
Clinical: Histamine skin wheal studies have shown a statistically and clinically significant antihistamine effect beginning at 1 hour and lasting in excess of 48 hours. After the discontinuation of the administration of a 5-day course treatment with Ebastine, the antihistamine activity remained apparent for more than 72 hours. This activity parallels the plasma levels of the main active acid metabolite, carebastine.
After repeated administration, inhibition of the peripheral receptors remained at a constant level, without tachyphylaxis. These results suggest that Ebastine at a dose of at least 10 mg produces a rapid, intense and long-lasting inhibition of peripheral H₁-histamine receptors, consistent with a once-a-day administration.
Sedation was studied through pharmaco-EEG, cognitive performance, visual-motor coordination tests and subjective estimates. There was no significant increase of sedation at the recommended dose. These results are consistent with those from double blind clinical trials. The incidence of sedation is comparable between placebo and Ebastine.
Pharmacokinetics: Ebastine is rapidly absorbed and undergoes extensive first pass metabolism following oral administration. Ebastine is almost totally converted to the pharmacologically active acid metabolite, carebastine.
After a single 10 mg oral dose, peak plasma levels of the metabolite occur at 2.6 to 4 hours and achieve levels of 80 to 100 ng/mL. The half-life of the acid metabolite is between 15 and 19 hours with 66% of the drug being excreted in the urine mainly as conjugated metabolites. Following the repeated administration of 10 mg once daily, steady state was achieved in 3 to 5 days with peak plasma levels ranging 130 to 160 ng/mL. In vitro studies with human liver microsomes show that Ebastine is metabolized to carebastine predominantly via the CYP3A4 pathway.
Concurrent administration of Ebastine with ketoconazole or erythromycin (both CYP3A4 inhibitors) to healthy volunteers was associated with significantly increased plasma concentrations of Ebastine and carebastine, especially with ketoconazole.
Both Ebastine and carebastine are highly protein bound 95%. In elderly subjects, no statistically significant changes were observed in the pharmacokinetics compared to those of young adult volunteers. In patients with renal insufficiency the elimination half-life of carebastine was increased to 23-26 hours. Similarly, in patients with hepatic insufficiency, the half-life is increased to 27 hours.

Ebastine is indicated for the treatment of seasonal/perennial allergic rhinitis and chronic urticaria.

Allergic rhinitis: Ebastine at a dose of 10 mg once a day is efficacious in the relief of the symptoms of allergic rhinitis; in patients with more severe symptoms including perennial allergic rhinitis, 20 mg once a day provides additional benefit.
Idiopathic chronic urticaria: The adult dose is 10 mg tablet once daily.
Special populations: A dosage of 10 mg daily should not be exceeded in patients with mild to moderate hepatic insufficiency. Ebastine 10 mg tablets are reserved for adults and children over 12 years of age.

In studies conducted at a high dosage, no clinically meaningful signs or symptoms were observed up to 100 mg once daily. There is no specific antidote for Ebastine. Gastric lavage, monitoring of vital functions including ECG and symptomatic treatment should be carried out.

Patients with known hypersensitivity to Ebastine or any of the tablet components. Patients with severe liver insufficiency.

Caution must be exercised when using Ebastine in patients known to be at cardiac risk such as those with long QT syndrome, hypokalemia, treatment with any drug known to produce an increase in QT interval or inhibit CYP3A4 enzyme systems such as azole antifungals and macrolide antibiotics.
Effects on Ability to Drive and Use of Machines: In man, psychomotor function has been investigated extensively and no effect was found at recommended therapeutic doses.
A study focused on car driving ability indicated that Ebastine did not induce any driving impairment even at 30 mg. Based on these results, Ebastine at recommended therapeutic doses does not affect the ability to drive or operate machines.
The cardiac effects of Ebastine alone have been investigated in clinical studies. No significant cardiac effects have been observed, in detailed analyses, at doses up to 100 mg per day (five times the recommended daily dose).

The safety of Ebastine during human pregnancy has not been established. Studies in rats and rabbits do not indicate any direct or indirect harmful effects with respect to the development of the embryo or fetus, or the course of gestation and peri- and post-natal development. No teratogenic effects have been identified in animals. However, there are no well-controlled studies in pregnant women and reproductive studies are not always predictive of human response. Therefore, Ebastine should be used during pregnancy only if clearly needed. It is not known whether Ebastine is excreted in human milk, therefore, Ebastine should not be used during lactation.

In clinical trials, the most commonly reported side effects with Ebastine were headache, dry mouth and drowsiness, which were comparable to placebo.
Other less commonly reported adverse events include: Pharyngitis, abdominal pain, dyspepsia, asthenia, epistaxis, rhinitis, sinusitis, nausea and insomnia.

The interaction of Ebastine in combination with either ketoconazole or erythromycin (both known to prolong the QTc interval) has been evaluated. Interaction has been observed with these combinations, resulting in higher Ebastine plasma levels but only in about a 10 msec increase in QTc greater than the increase seen with ketoconazole or erythromycin alone.
When Ebastine is administered with food, there is a 1.5 to 2.0 fold increase in the plasma levels and the AUC of the main active acid metabolite of Ebastine. This increase does not alter the T_max. The administration of Ebastine with food does not cause a modification in its clinical effect.

Store at temperatures not exceeding 30°C. Protect from light.

Antihistamines & Antiallergics

R06AX22 - ebastine ; Belongs to the class of other antihistamines for systemic use.

Rx