kestine

SCHEDULING STATUS:
S2

PROPRIETARY NAME
(and dosage form):

KESTINE®
Tablets

COMPOSITION:
Each film-coated tablet contains 10 mg ebastine.

PHARMACOLOGICAL CLASSIFICATION:
A 5.7.1 Medicines affecting autonomic functions - Antihistamines

PHARMACOLOGICAL ACTION:
Ebastine is a long-acting and selective H1-histamine receptor antagonist. After repeated administration, inhibition of peripheral receptors remain at a constant level.
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 carebastine occur at 2,6 to 4 hours and achieve levels of 80 to 100 ng/mL. The half-life of carebastine is between 15 and 19 hours with 66% of the medicine being excreted in the urine mainly as conjugated metabolites. Following repeated administration of 10 mg once daily, steady state is 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 metabolised 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 concentration and elimination half-life of ebastine and carebastine. With ketoconazole the Cmax and AUC were 15 times and 40 times respectively increased, with erythromycin the values were doubled.
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 increased to 27 hours.

INDICATIONS:
Ebastine is indicated for the symptomatic treatment of:
•    Seasonal and perennial allergic rhinitis
•    Idiopathic chronic urticaria

CONTRA-INDICATIONS:
Patients with a known hypersensitivity to ebastine or any of its ingredients.
The safety of ebastine during pregnancy and lactation has not been established.
The safety and efficacy of ebastine tablets in children less than 12 years has not been established.

WARNINGS:
It is advisable to exercise caution when using Kestine in patients known to have the following conditions: long QT syndrome, hypokalaemia, treatment with any medicine known to produce an increase in QT interval or inhibit CYP3A4 enzyme systems such as azole antifungals and macrolide antibiotics (refer to section on "Interactions").

DOSAGE AND DIRECTIONS FOR USE:
Allergic rhinitis
10 mg (one tablet) once a day
Idiopathic chronic urticaria
10 mg (one tablet) once a day.
Ebastine may be taken with or without food.

SIDE-EFFECTS AND SPECIAL PRECAUTIONS:
The most common side-effects are headache, dry mouth and drowsiness. Other less commonly reported side effects include pharyngitis, abdominal pain, dyspepsia, asthenia, epistaxis, rhinitis, sinusitis, nausea and insomnia.
Interactions:
The interaction of ebastine in combination with either ketoconazole or erythromycin (both known to prolong the QTc interval) has been evaluated. A significant pharmacokinetic and pharmacodynamic interaction has been observed with these combination; an 18-19 msec (4,7% - 5%) increase in QTc has been reported with either combination.
Ebastine does not interact with the kinetics of theophylline, warfarin, cimetidine, diazepam or alcohol.
The sedation effect of alcohol and diazepam may be enhanced.
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 Tmax. The administration of ebastine with food does not cause a modification in its clinical effect.
Ebastine lacks significant sedative effects. Patients should, however, be warned that a small number of individuals may experience sedation. It is therefore advisable to determine individual response before driving or performing complicated tasks. This effect may be compounded by the simultaneous intake of alcohol or other central nervous system depressants.

KNOWN SYMPTOMS OF OVERDOSAGE AND PARTICULARS OF ITS TREATMENT:
In studies conducted at a high dosage, no clinically meaningful signs or symptoms were observed up to 100 mg given once daily. There is not specific antidote for ebastine.
In case of accidental overdosages, gastric lavage, monitoring of vital functions including ECG, and symptomatic treatment should be carried out.

IDENTIFICATION:
Round, white, film-coated tablets marked E10 and a score line on the same side.

PRESENTATION:
Packs containing 10 or 30 tablets.

STORAGE INSTRUCTIONS:
Store below 25°C.
Protect from light.
KEEP OUT OF REACH OF CHILDREN.

REGISTRATION NUMBER:
29/5.7.1/0344

NAME AND BUSINESS ADDRESS OF THE APPLICANT:
Pharmacare Ltd
7 Fairclough Road,
Korsten
Port Elizabeth 6020

DATE OF PUBLICATION OF THIS PACKAGE INSERT:
24 October 1997

Under licence from:
{logo} Almirall Prodesfarma

51165200-9/98        511772A