Active ingredients: Ebastine
KESTINE 10 mg film-coated tablets
Kestine package inserts are available for pack sizes:- KESTINE 10 mg film-coated tablets
- KESTINE 20 mg film-coated tablets
- KESTINE 10 mg oral lyophilisate
- KESTINE 20 mg oral lyophilisate
- KESTINE 1 mg / ml syrup
Why is Kestine used? What is it for?
Antihistamines for systemic use.
Ebastine is indicated in the symptomatic treatment of:
- Allergic rhinitis (seasonal or perennial) associated or not with allergic conjunctivitis.
- Urticaria
Contraindications When Kestine should not be used
Do not take Kestine 10 mg coated tablets
- if you are allergic to ebastine or any of the other ingredients of this medicine
- Severe hepatic insufficiency.
- Children under the age of 12.
- Generally contraindicated in pregnancy and lactation (see section "Pregnancy, lactation and fertility").
Precautions for use What you need to know before taking Kestine
Talk to your doctor or pharmacist before taking Kestine 10 mg coated tablets.
Use caution in the use of ebastine in patients with known cardiac risk, such as those with prolonged QT interval syndrome, hypokalaemia, who are being treated with drugs that induce an increase in the QT interval or that inhibit the CYP3A4 enzyme system such as azole antifungals, such as ketoconazole and itraconazole, and macrolide antibiotics such as erythromycin (see section "Taking other medicines").
Use caution if you are being treated with anti-tuberculosis drugs such as rifampicin (see section "Taking other medicines").
Ebastine should be used with caution in patients with renal insufficiency or mild or moderate hepatic insufficiency (see section "How to take Kestine 10 mg coated tablets").
Interactions Which drugs or foods may change the effect of Kestine
Tell your doctor if you are taking or have recently taken or may take other medicines.
Interactions of ebastine in combination with ketoconazole or erythromycin (both known to prolong the QTc interval of the electrocardiogram) have been evaluated. With these combinations, interactions have been observed resulting in an increase in ebastine plasma levels but a prolongation of the QTc interval of only about 10 msec greater than that seen with ketoconazole or erythromycin alone.
Pharmacokinetic interactions have been observed when ebastine is taken concomitantly with rifampicin; these interactions may result in lower plasma concentrations and reduced antihistamine effects.
No interactions of ebastine with theophylline, warfarin, cimetidine, diazepam or alcohol have been reported.
Taking ebastine with food does not interfere with its clinical effect.
Warnings It is important to know that:
Pregnancy, breastfeeding and fertility
If you are pregnant or breastfeeding, think you may be pregnant or are planning to become pregnant, ask your doctor or pharmacist for advice before taking this medicine.
Fertility
There are no data on fertility in humans.
Pregnancy
Only limited data are available on the use of ebastine in pregnant women. Animal studies do not indicate direct or indirect harmful effects on reproductive toxicity. As a precautionary measure, it is preferable to avoid the use of ebastine during pregnancy.
Feeding time
It is not known whether ebastine is excreted in human milk. As a precautionary measure, avoid using ebastine while breastfeeding
Effects on ability to drive and use machines
Ebastine, at the recommended doses, did not produce negative effects on driving and use of machinery. Nevertheless, it is recommended to check the individual reaction to the use of ebastine before carrying out complex activities: drowsiness and dizziness may occur. Read the "Possible Side Effects" section.
Important information about some of the ingredients
Kestine 10 mg coated tablets contain lactose. If your doctor has diagnosed an intolerance to some sugars, contact your doctor before taking this medicine.
Dose, Method and Time of Administration How to use Kestine: Posology
Always take this medicine exactly as your doctor or pharmacist has told you. Consult your doctor or pharmacist if you are unsure.
The use of Kestine 10 mg coated tablets is reserved for adults and children over 12 years of age.
- Allergic rhinitis:
At doses of 10 mg once daily, ebastine is effective in relieving the symptoms of allergic rhinitis; in patients with more severe symptoms, including perennial allergic rhinitis, 1 single dose of 20 mg once daily may be higher. benefit.
- Urticaria:
The adult dose is 10 mg once a day. Ebastine can be taken with or without meals.
In patients with mild or moderate hepatic insufficiency it is recommended not to exceed the daily dosage of 10 mg.
The safety and efficacy in children below 12 years of age have not been studied.
Overdose What to do if you have taken too much Kestine
In studies conducted with high doses, up to 100 mg administered once daily, no clinically significant signs or symptoms were observed.
There is no specific antidote to ebastine. Gastric lavage, monitoring of vital functions, including ECG, and symptomatic treatment will eventually need to be performed.
In case of accidental ingestion / intake of an overdose of Kestine, notify your doctor immediately or go to the nearest hospital.
If you forget to take Kestine 10 mg coated tablets
Do not take a double dose to make up for a forgotten tablet. Ask your doctor or pharmacist if you need more information on how to use this medicine.
Side Effects What are the side effects of Kestine
Like all medicines, Kestine can cause side effects, although not everybody gets them.
The following adverse reactions have been reported in clinical trials and post-marketing experience.
Very common (may affect more than 1 in 10 people)
- headache
Common (may affect up to 1 in 10 people)
- drowsiness
- dry mouth
Rare (may affect up to 1 in 1000 people):
- hypersensitivity reactions (such as anaphylaxis and angioedema)
- nervousness, insomnia
- dizziness, reduced sense of touch, reduced or altered sense of taste
- palpitations, tachycardia
- vomiting, abdominal pain, nausea, digestive problems
- liver problems, abnormal liver function tests (increased transaminases, gamma-GT, alkaline phosphatase and bilirubin)
- urticaria, rash, dermatitis
- menstrual disturbances
- edema, asthenia
Reporting of side effects.
If you get any side effects, including any possible side effects not listed in this leaflet, contact your doctor or pharmacist. Undesirable effects can also be reported directly via the national reporting system at "https://www.aifa.gov.it/content/segnalazioni-reazioni-avverse". By reporting undesirable effects you can help provide more information on the safety of this medicine
Expiry and Retention
See the expiration date printed on the package. This date refers to the product in intact and correctly stored packaging.
Store at a temperature not exceeding 30 ° C. Protect from light.
WARNING: do not use the medicine after the expiry date indicated on the package. The expiry date is relative to the last day of the month.
Keep this medicine out of the sight and reach of children.
Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines you no longer use. This will help protect the environment.
Contents of the pack and other information
What Kestine 10 mg coated tablets contain
Each tablet contains:
Active ingredient: ebastine 10 mg.
Other ingredients (excipients) are:
Core: microcrystalline cellulose, lactose, pregelatinised maize starch, croscarmellose sodium, magnesium stearate.
Coating: hypromellose, macrogol 6000, titanium dioxide.
Description of the appearance and contents of the package
Film-coated tablets. Cartons of 5, 10, 15, 20 and 30 tablets
Source Package Leaflet: AIFA (Italian Medicines Agency). Content published in January 2016. The information present may not be up-to-date.
To have access to the most up-to-date version, it is advisable to access the AIFA (Italian Medicines Agency) website. Disclaimer and useful information.
01.0 NAME OF THE MEDICINAL PRODUCT
KESTINE TABLETS COATED WITH FILM
02.0 QUALITATIVE AND QUANTITATIVE COMPOSITION
Kestine 10 mg film-coated tablets
One tablet contains:
Active ingredient: Ebastine 10mg
Excipients with known effect: Lactose 88.5 mg
Kestine 20 mg film-coated tablets
One tablet contains: Active ingredient: Ebastine 20mg
Excipients with known effect: Lactose 177 mg
For the full list of excipients, see section 6.1
03.0 PHARMACEUTICAL FORM
Film-coated tablets.
04.0 CLINICAL INFORMATION
04.1 Therapeutic indications
Ebastine is indicated in the symptomatic treatment of:
Allergic rhinitis (seasonal or perennial) associated or not with allergic conjunctivitis.
Urticaria (indication authorized for Kestine 10 mg only)
04.2 Posology and method of administration
Kestine 10 mg film-coated tablets
Allergic rhinitis:
At doses of 10 mg once daily, ebastine is effective in relieving the symptoms of allergic rhinitis; in patients with more severe symptoms, including perennial allergic rhinitis, 1 single dose of 20 mg once daily may be higher. benefit.
Urticaria:
The adult dose is 10 mg once a day.
Populations details
In patients with mild or moderate hepatic insufficiency it is recommended not to exceed the daily dosage of 10 mg.
Population pediatric
The safety and efficacy in children below 12 years of age have not been studied.
Kestine 20 mg film-coated tablets
Allergic rhinitis:
At doses of 20 mg once daily, ebastine is effective in relieving the symptoms of severe allergic rhinitis. A single dose of 10 mg once daily is recommended in patients with less severe symptoms.
Populations details
In patients with mild or moderate hepatic insufficiency it is recommended not to exceed the daily dosage of 10 mg.
Population pediatric
The use of Kestine 20 mg tablets is reserved for adults and children over 12 years of age.
Method of administration
Ebastine can be taken with or without meals
04.3 Contraindications
Hypersensitivity to the active substance or to any of the excipients. Severe hepatic insufficiency
Children under the age of 12.
Generally contraindicated in pregnancy and lactation (see section 4.6).
04.4 Special warnings and appropriate precautions for use
Use caution in the use of ebastine in patients with known cardiac risk, such as those with prolonged QT interval syndrome, hypokalaemia, who are being treated with drugs that induce an increase in the QT interval or that inhibit the CYP3A4 enzyme system, such as azole antifungals such as ketoconazole and itraconazole and macrolide antibiotics such as erythromycin (see section 4.5).
As there are pharmacokinetic interactions with antituberculous agents such as rifampicin (see section 4.5), care should be taken when prescribing ebastine with drugs in this group.
Ebastine should be used with caution in patients with renal insufficiency or mild or moderate hepatic insufficiency (see sections 4.2 and 5.2).
This medicinal product contains lactose: Patients with rare hereditary problems of galactose intolerance, the Lapp Lactase deficiency or glucose-galactose malabsorption should not take this medicine.
04.5 Interactions with other medicinal products and other forms of interaction
The interactions of ebastine in combination with ketoconazole or erythromycin (both known to prolong the QTc interval) have been evaluated. With these combinations, interactions have been observed resulting in an increase in ebastine plasma levels but a prolongation of the QTc interval of only about 10 msec greater than that seen with ketoconazole or erythromycin alone.
Pharmacokinetic interactions have been observed when ebastine is taken concomitantly with rifampicin; these interactions may result in lower plasma concentrations and reduced antihistamine effects.
No interactions of ebastine with theophylline, warfarin, cimetidine, diazepam or alcohol have been reported.
When ebastine is administered with food, a 1.5 to 2-fold increase in plasma levels and AUC of the main active acid metabolite of ebastine is observed. This increase does not alter the Tmax value. Taking ebastine with food does not interfere with its clinical effect.
04.6 Pregnancy and lactation
Fertility
There are no data on fertility in humans during treatment with ebastine.
Pregnancy
Only limited data are available on the use of ebastine in pregnant women. Animal studies do not indicate direct or indirect harmful effects on reproductive toxicity. As a precautionary measure, it is preferable to avoid the use of ebastine during pregnancy.
Feeding time
It is not known whether ebastine is excreted in human milk. The high protein binding of ebastine and its major metabolite carebastine (> 97%) suggests that there should be no excretion of the drug in human milk. As a precautionary measure, avoid the use of ebastine during lactation.
04.7 Effects on ability to drive and use machines
Psychomotor functions have been extensively studied in humans and no effect has been found. Ebastine at recommended therapeutic doses does not affect the ability to drive and use machines. However, in sensitive patients who react unusually to ebastine, it is better to evaluate individual reactions before the patient drives or uses machines: drowsiness or dizziness may occur (see section 4.8).
04.8 Undesirable effects
From the analysis of data on 5,708 patients treated with ebastine in various clinical trials versus placebo, it was found that the most frequent adverse reactions were dry mouth and somnolence.
Adverse reactions reported by children (n = 460) in clinical studies are similar to those seen in adults.
The table below lists the adverse reactions reported in clinical and post-marketing studies according to the convention: very common (≥1 / 10), common (≥1 / 100 to
Reporting of suspected adverse reactions.
Reporting of suspected adverse reactions occurring after authorization of the medicinal product is important as it allows continuous monitoring of the benefit / risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the national reporting system. "address https://www.aifa.gov.it/content/segnalazioni-reazioni-avverse
04.9 Overdose
In studies conducted with high doses, up to 100 mg administered once daily, no clinically significant signs or symptoms were observed.
There is no specific antidote to ebastine. Gastric lavage, monitoring of vital functions, including ECG, and symptomatic treatment will eventually need to be performed.
05.0 PHARMACOLOGICAL PROPERTIES
05.1 Pharmacodynamic properties
Pharmacotherapeutic group: Antihistamines for systemic use Code
ATC: R06AX22
Preclinical results
Ebastine produces a rapid and long-lasting inhibition of the effects induced by histamine and has a strong affinity for H1 receptors. After oral administration neither ebastine nor its metabolites cross the blood brain barrier. This characteristic is related to the low sedative effect observed. in experimental studies on the action of ebastine on the central nervous system.
In vitro and in vivo, ebastine has been shown to be a potent, long-lasting and highly selective antagonist of histamine H1 receptors, free from undesirable CNS actions and anticholinergic effects.
Clinical results
Skin edema tests have shown a statistically and clinically significant anti-histamine effect which appears after 1 hour and lasts for over 48 hours.
After discontinuation of ebastine administration for 5 days of treatment, antihistamine activity persists for more than 72 hours. This activity correlates with plasma levels of the major active acid metabolite carebastine.
After repeated administration, inhibition of peripheral receptors remains at constant levels, without tachyphylaxis. These results suggest that ebastine at doses of at least 10 mg produces a rapid, intense and long-lasting, compatible inhibition of peripheral H1 receptors for histamine. with a once daily administration.
Sedation was studied using drug-EEG tests, cognitive performance, visual-motor coordination, and subjective estimates. There is no significant increase in sedation at recommended doses. These results agree with those of the double-blind clinical studies: the incidence of sedation was comparable in the ebastine or placebo groups. The cardiac effects of ebastine have been investigated in various clinical studies. At the recommended doses, no cardiac effects were observed, including prolongation of the QT interval. In subjects with no additional risk factors, at repeated doses up to 100 mg daily or single doses of 500 mg, a modest increase in heart rate of a few beats per minute resulted in shortening of the QT interval, but no significant change in QTc.
Chronic idiopathic urticaria has been studied as a clinical model for all forms of urticaria because, in all forms, the pathophysiology is similar regardless of etiology and because, in perspective, it is easier to recruit chronic patients. it is a causal factor in all forms of urticaria, in accordance with what is reported in clinical guidelines, ebastine is believed to be effective in improving symptoms in all types of urticaria and not only in chronic idiopathic.
05.2 Pharmacokinetic properties
Ebastine is rapidly absorbed and undergoes extensive first pass metabolism following oral administration.
Ebastine is almost totally transformed into its pharmacologically active acid metabolite, carebastine.
After a single dose of 10 mg orally, the plasma peak of the metabolite is observed after 2.6 - 4 hours and reaches levels between 80 and 100 ng / ml. The half-life of the acid metabolite is 15 - 19 hours and 66% of the drug is excreted in the urine mainly in the form of conjugated metabolites. After repeated administration of 10 mg once a day, the equilibrium state is reached in 3 - 5 days with plasma peaks between 130 and 160 ng / ml.
After a single oral dose of 20 mg, plasma peaks of ebastine (mean value 2.8 ng / ml) are reached in 1-3 hours. The plasma peaks of the metabolic carebastine reach a mean value of 157 ng / ml.
Education in vitro on human liver microsomes showed that ebastine is metabolised to carebastine predominantly via the CYP3A4 enzyme system. Co-administration of ebastine and ketoconazole or erythromycin (both CYP3A4 inhibitors) to healthy volunteers was associated with significantly increased plasma concentrations of ebastine and carebastine (see section 4.5).
Both ebastine and carebastine are more than 97% protein bound.
No statistically significant pharmacokinetic changes were observed in elderly subjects compared to young adult volunteers.
In patients with renal insufficiency the elimination half-life of carebastine is increased to 23 - 26 hours. Similarly in patients with hepatic insufficiency the half-life is increased to 27 hours.
05.3 Preclinical safety data
Non-clinical data reveal no significant toxic effects based on conventional studies of safety pharmacology, repeated dose toxicity, genotoxicity, carcinogenic potential and reproductive toxicity.
06.0 PHARMACEUTICAL INFORMATION
06.1 Excipients
- Core: Microcrystalline cellulose, Lactose, Pregelatinised maize starch, Croscarmellose sodium, Magnesium stearate.
- Coating: Hypromellose, Macrogol 6000, Titanium dioxide.
06.2 Incompatibility
None known.
06.3 Period of validity
Kestine 10 mg film-coated tablets: 3 years
Kestine 20 mg film-coated tablets: 3 years
The period of validity indicated refers to the product in intact packaging, correctly stored.
06.4 Special precautions for storage
Kestine 10 mg film-coated tablets
Protect from light.
Store at a temperature not exceeding 30 ° C
Kestine 20 mg film-coated tablets
Store at a temperature not exceeding 30 ° C
06.5 Nature of the immediate packaging and contents of the package
Kestine 10 mg film-coated tablets
PVC / Aluminum blister.
Box of 30 tablets of 10 mg -
Kestine 20 mg film-coated tablets
PVC / Aluminum blister.
Box of 20 tablets of 20 mg -
06.6 Instructions for use and handling
No special instructions
Unused medicine and wastes derived from this medicine must be disposed of in accordance with local regulations.
07.0 MARKETING AUTHORIZATION HOLDER
ALMIRALL SpA
Via Messina, 38 Torre C
20154 Milan
08.0 MARKETING AUTHORIZATION NUMBER
KESTINE 10 mg coated tablets, 30 tablets AIC N ° 034930014
KESTINE 10 mg coated tablets, 5 tablets AIC N ° 034930040
KESTINE 10 mg coated tablets, 10 tablets AIC N ° 034930053
KESTINE 10 mg coated tablets, 15 tablets AIC N ° 034930065
KESTINE 10 mg coated tablets, 20 tablets AIC N ° 034930077
KESTINE 20 mg coated tablets, 5 tablets AIC N ° 034930091
KESTINE 20 mg coated tablets, 10 tablets AIC N ° 034930103
KESTINE 20 mg coated tablets, 15 tablets AIC N ° 034930089
KESTINE 20 mg coated tablets, 20 tablets AIC N ° 034930026
KESTINE 20 mg coated tablets, 30 tablets AIC N ° 034930038
09.0 DATE OF FIRST AUTHORIZATION OR RENEWAL OF THE AUTHORIZATION
Kestine 10 mg film-coated tablets: December 2001 - Renewal 2006
Kestine 20 mg film-coated tablets: June 2003 - Renewal 2006
