EBASTINE BIOGARAN 10 mg Cpr pell Plq/15

Ebastine......................................................................................................................................................... 10 mg

For a film-coated tablet.

Excipient with known effect: each tablet contains 88,70 mg of lactose monohydrate.

Symptomatic treatment of:

• seasonal and perennial allergic rhinitis,
• urticaria.

Dosage

Reserved for adults and children over 12 years:

• seasonal and perennial allergic rhinitis: 10 to 20 mg per day as 1 daily intake, during or outside meals,
• urticaria: 10 mg per day as 1 daily intake, during or outside meals.

Special populations

Dose adjustment is not necessary in patients with mild, moderate or severe renal impairment or mild to moderate hepatic impairment. There is no experience with doses above 10 mg in patients with severe hepatic impairment. Therefore, the dose of 10 mg must not be exceeded in patients with severe hepatic impairment. Treatment should be continued until symptoms disappear.

Method of administration

Oral use.

• Children under 12 years in the absence of efficacy and safety data,
• Hypersensitivity to the active substance or to any of the excipients listed in section Composition.

The prescription of ebastine should be cautious in patients with long QT syndrome, with hypokalaemia, or receiving a medicine known to prolong the QT interval or to inhibit CYP3A4, such as azole antifungals such as ketoconazole and itraconazole or macrolides such as erythromycin (see section Interactions).

As there is a pharmacokinetic interaction between antituberculous medicines such as rifampicin (see section Interactions), caution is required when co-prescribing ebastine with molecules from this group.

Ebastine should be used with caution in patients with severe hepatic impairment (see section Dosage and administration).

This medicine contains lactose. Patients with galactose intolerance, total lactase deficiency or glucose-galactose malabsorption syndrome (rare hereditary diseases) must not take this medicine.

Combinations not recommended

Pharmacokinetic interactions have been observed when ebastine was given with ketoconazole, or itraconazole and erythromycin. These interactions result in an increase in plasma concentrations of ebastine and, to a lesser extent, of carebastine, which were nevertheless not associated with any significant clinical consequence. However, as a precaution, combination with ketoconazole, itraconazole, erythromycin, clarithromycin, josamycin should be avoided: increased risk of occurrence of ventricular rhythm disorders in predisposed subjects (congenital long QT syndrome).

Pharmacokinetic interactions have been observed when ebastine was given with rifampicin. These interactions may lead to lower plasma concentrations of ebastine and reduce the antihistamine effect.

No interaction has been reported between ebastine and theophylline, warfarin, cimetidine, diazepam and alcohol.

Administration of ebastine with food does not modify its clinical effect.

Pregnancy

There is little data on the use of ebastine in pregnant women. Animal toxicity studies do not show direct or indirect harmful effects. As a precaution, it is preferable not to use ebastine during pregnancy.

Breast-feeding

It is not known whether ebastine is excreted in human milk or not. The high level of protein binding of ebastine (97 %) and its main metabolite, carebastine, suggests that there is no excretion into breast milk. As a precaution, it is preferable not to use ebastine during breastfeeding.

Fertility

There is no fertility data with ebastine in humans.

In humans, psychomotor function has been widely studied and no effect has been found. Ebastine at the recommended therapeutic doses does not affect the ability to drive vehicles and use machines.

However, in sensitive subjects who react unusually to ebastine, it is advised to know individual reactions before the patient drives or performs complex activities: drowsiness and dizziness may occur (see section Adverse effects).

In a pooled analysis of placebo-controlled clinical trials with 5 708 patients on ebastine, the most frequently reported adverse effects were dry mouth and drowsiness. Treatment-related adverse effects in clinical trials in children (n=460) were similar to those observed in adults.

The table below lists the adverse effects reported in clinical trials and since marketing, according to the following convention: very common (≥1/10), common (≥1/100 and <1/10), uncommon (≥1/1000 and <1/100), rare (≥1/10 000 and <1/1000), very rare (<1/10 000) and frequency not known (cannot be estimated from the available data).

Reporting of suspected adverse reactions

Reporting of suspected adverse effects after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Health professionals should report any suspected adverse effects via the national reporting system: Agence nationale de sécurité du médicament et des produits de santé (ANSM) and the network of Regional Centres of Pharmacovigilance - Website: www.signalement-sante.gouv.fr.

In studies conducted with high dosage, no significant clinical signs or symptoms were observed up to 100 mg per day.

Management in case of massive overdose:

• no antidote is known to date,
• gastric evacuation,
• symptomatic treatment,
• monitoring of vital functions including ECG monitoring.

Pharmacotherapeutic class, ATC code: R06AX22.

Ebastine and its active metabolite, carebastine, are selective antihistamines acting on peripheral H1 receptors, which appear to be devoid of sedative and anticholinergic side effects at the recommended doses.

Ebastine is rapidly absorbed after oral administration and undergoes a very extensive intestinal and hepatic first-pass effect. It is almost entirely converted into its pharmacologically active acid metabolite, carebastine.

After a single oral dose of 10 mg, the peak plasma concentration is reached after 2 to 4 hours, with levels ranging between 80 and 100 ng/ml.

In vitro studies on human liver microsomes show that ebastine is metabolised mainly to carebastine via the cytochrome CYP3A4.

The half-life of the acid metabolite is between 15 and 19 hours, with urinary excretion of 66%, mainly as the conjugated metabolite. After repeated administration of ebastine at a dose of 10 mg once daily, steady state is reached in 3 to 5 days, with peak plasma concentrations ranging from 130 to 160 ng/ml.

Ebastine and carebastine are strongly bound to plasma proteins, with a binding rate greater than 97%.

The passage of ebastine and its active metabolite, carebastine, across the blood-brain barrier is very low.

Passage into breast milk has not been studied.

Elderly subject

The pharmacokinetic parameters do not differ in a statistically significant way from the values recorded in young adults.

Renal and hepatic impairment

In patients with mild, moderate or severe renal impairment treated with a daily dose of ebastine of 20 mg, as well as in patients with mild to moderate hepatic impairment treated with a daily dose of ebastine of 20 mg, or in patients with severe hepatic impairment treated with a daily dose of ebastine of 10 mg, the concentrations of ebastine and carebastine reached between day 1er and day 5th day of treatment were similar to those observed in healthy volunteers. Consequently, the pharmacokinetic profile of ebastine and its metabolite does not change significantly in patients with varying degrees of renal or hepatic impairment.

4 years.

This medicine does not require any particular storage precautions.

No special requirements.