Co-Aleva

Each tablet contains: Ebastine 10 mg, Betamethasone (as Sodium Phosphate) 500 mcg.

Antihistamine/Corticosteroid.
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 nor 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 from 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.
Corticosteroids like Betamethasone are readily absorbed from the gastrointestinal tract. It is rapidly distributed to all body tissues. They cross the placenta to varying degrees and may be excreted in small amounts in breast milk. Most corticosteroids in the circulation are extensively bound to plasma proteins, mainly to globulin and less so to albumin. The corticosteroid-binding globulin has high affinity but low binding capacity. The synthetic corticosteroids are less extensively protein bound than hydrocortisone. They also tend to have longer half-lives. Corticosteroids are metabolized mainly in the liver but also in other tissues and are excreted in the urine. The slower metabolism of synthetic corticosteroids with their lower protein-binding affinity may account for their increased potency compared with the natural corticosteroids.

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

Adult Dose: 1 tablet (Ebastine 10 mg + Betamethasone 500 mcg) twice daily. Or as prescribed by a physician.

In studies conducted at a high dosage, no clinically meaningful signs or symptoms were observed up to 100 mg given once daily. There is no specific antidote for Ebastine. Gastric lavage, monitoring of vital functions including ECG and symptomatic treatment should be carried out.
Large doses of Betamethasone may produce Cushingoid symptoms typical of hyperactivity of the adrenal cortex, with moon-face, sometimes with hirsutism, buffalo hump, flushing, increased bruising, ecchymoses, striae and acne.

Patients with a known hypersensitivity to Ebastine, Betamethasone or any of the tablet ingredients. 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.
Betamethasone should only be used systematically with great caution in the presence of heart failure, recent myocardial infarction or hypertension, in patients with diabetes mellitus, epilepsy, glaucoma, hypothyroidism, hepatic failure, osteoporosis, peptic ulceration, psychoses or severe affective disorders and renal impairment.
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.
Although some adverse effects have been recorded and certain precautions need to be observed regarding the use of Betamethasone during pregnancy they may appropriately be given during pregnancy to promote fetal maturation where there is a risk of premature delivery. In addition, in those maternal conditions serious enough to require administration of Betamethasone the risk to both mother and offspring of discontinuing therapy is often greater than that of Betamethasone administration during pregnancy.

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 of Ebastine include: Pharyngitis, abdominal pain, dyspepsia, asthenia, epistaxis, rhinitis, sinusitis, nausea and insomnia.
Betamethasone has little or no effects on sodium and water retention.
Adverse effects of Betamethasone should be treated symptomatically, with the dosage reduced or slowly withdrawn where possible.

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.
Concurrent use of barbiturates, carbamazepine, phenytoin, primidone or rifampicin may enhance the metabolism and reduce the effects of systemic corticosteroids. Conversely oral contraceptives or ritonavir may increase plasma concentrations of corticosteroids. Use of corticosteroids with potassium-depleting diuretics, such as thiazides and furosemide may cause excessive potassium loss. There is also an increased risk of hypokalemia with concurrent amphotericin B or bronchodilator therapy with xanthines or beta 2-agonists. There may be increased incidence of gastrointestinal bleeding and ulceration when corticosteroids are given with NSAIDs. Response to anticoagulants may be altered by corticosteroids and requirements of antidiabetic drugs and antihypertensives may be increased. Corticosteroids may decrease serum concentrations of salicylates and may decrease the effect of antimuscarinics in myasthenia gravis.

Store at a temperature not exceeding 30°C. Protect from light.

Antihistamines & Antiallergics

R06AX - Other antihistamines for systemic use ; Used as systemic antihistamines.

Rx