Zaditen - Package Leaflet

Indications Contraindications Precautions for use Interactions Warnings Dosage and method of use Overdose Undesirable Effects Shelf life and Storage Composition and pharmaceutical form

Active ingredients: Ketotifene (Ketotifene acid fumarate)

ZADITEN 2 mg PROLONGED-RELEASE TABLETS

Zaditen package inserts are available for pack sizes:
  • ZADITEN 2 mg PROLONGED-RELEASE TABLETS
  • ZADITEN 0.2 mg / mL SYRUP
  • ZADITEN 0.25 mg / mL, eye drops, solution

Why is Zaditen used? What is it for?

PHARMACOTHERAPEUTIC CATEGORY

Antiallergic - antihistamine.

THERAPEUTIC INDICATIONS

Symptomatic treatment of allergic rhinitis.

Contraindications When Zaditen should not be used

Known hypersensitivity to ketotifen or to any of the excipients (see "List of excipients"); epilepsy; patients being treated with oral antidiabetic drugs; breastfeeding.

Precautions for use What you need to know before you take Zaditen

Ketotifen does not prevent or cure acute asthma attacks.

Medicines already in use for the treatment of asthma symptoms and its prevention must in no way be stopped suddenly, if long-term treatment with ZADITEN is started. This is especially true when the treatment is based on cortisone drugs, as steroid-dependent patients may be affected by adrenocortical insufficiency; in this case it may take up to a year for the recovery of a normal pituitary-adrenal stress response.

Thrombocytopenia may occur in patients taking ZADITEN concomitantly with oral antidiabetics. Concomitant administration of these drugs is therefore to be avoided. Seizures have been reported very rarely during ZADITEN therapy. Since ZADITEN may lower the seizure threshold, it should be used carefully in patients with a history of epilepsy. In case of decreased attention due to the sedative effect of ZADITEN, the dose will have to be reduced.

Monitor for signs of severe sleepiness. The onset of somnolence, especially in the first days of therapy, may impair some practical skills, such as driving or working with machines (see also "Effects on the ability to drive and" use machines ").

The use of alcoholic beverages and central nervous system depressants (eg sedatives-hypnotics, other antihistamines) is not recommended during therapy. The prolonged-release coated tablets contain lactose.

Interactions Which drugs or foods can change the effect of Zaditen

Tell your doctor or pharmacist if you have recently taken any other medicines, even those without a prescription. ZADITEN can increase the effects of drugs that depress the central nervous system, antihistamines, anticoagulants and alcohol.

The concomitant administration of oral antidiabetic agents and ZADITEN should be avoided as thrombocytopenia may occur (see "Precautions for use"). Ketotifen amplifies the effects of any co-administered bronchodilators, whose frequency of use should be appropriately reduced.

Warnings It is important to know that:

This medicine is not recommended for use in patients with rare hereditary conditions such as lactose intolerance, severe lactase deficiency or glucose-galactose malabsorption.

Use during pregnancy and lactation

Ask your doctor or pharmacist for advice before taking any medicine.

Pregnancy

Although no effects on pregnancy or postnatal development were observed in animals at maternal tolerated dosage levels, the safety of ketotifen in human pregnancy has not been established. ZADITEN should therefore only be given to pregnant women if conditions dictate it.

Feeding time

Ketotifen is excreted in the breast milk of rats. Since it is also supposed to be excreted in humans, mothers treated with ZADITEN should not breastfeed.

Effects on ability to drive and use machines

In the first days of therapy with ZADITEN the patient's ability to react may be reduced; therefore, caution is required when driving vehicles or using machines.

Dosage and method of use How to use Zaditen: Dosage

Adults: 2 mg once a day, preferably in the evening; if necessary, 2 mg twice daily (morning and evening, 12 hour interval).

Children over 3 years: 2 mg once a day, preferably in the evening.

ZADITEN 2 mg prolonged-release tablets should be swallowed whole.

Overdose What to do if you have taken too much Zaditen

Among the major symptoms of acute overdose we find: drowsiness which can lead to severe sedation; dizziness, confusion and disorientation; bradycardia or tachycardia and hypotension; hyperexcitability or convulsions especially in children; wheezing or respiratory depression; reversible coma. Treatment is symptomatic. Emesis is not recommended due to the risk of seizures. If the drug has been taken recently, stomach emptying may be considered, gastric lavage and the administration of activated charcoal may be considered.

Symptomatic treatment and monitoring of the cardiovascular system are recommended if necessary; if excitation or convulsions are present, benzodiazepines or short-acting barbiturates may be administered. ZADITEN is not eliminated by dialysis.

In case of accidental ingestion / intake of an excessive dose of ZADITEN, notify your doctor immediately or go to the nearest hospital.

If you have any questions about the use of ZADITEN, ask your doctor or pharmacist.

Side Effects What are the side effects of Zaditen

Like all medicines, ZADITEN can cause side effects, although not everybody gets them.

Adverse reactions are listed in Table 1 in order of frequency (most frequent first) and according to the following characteristics: very common (≥ 1/10); common (≥ 1/100,

Table 1

Infections and infestations

Uncommon: cystitis.

Disorders of the immune system

Very rare: erythema multiforme, Stevens-Johnson syndrome, severe skin reaction.

Diseases of metabolism and nutrition

Rare: weight gain.

Psychiatric diseases

Common: state of excitement, irritability, insomnia, nervousness.

Diseases of the nervous system

Uncommon: dizziness.

Rare: sedation.

Gastrointestinal affections

Uncommon: dry mouth.

Hepatobiliary affections

Very rare: hepatitis, increased liver enzymes.

Somnolence, sedation, dry mouth and dizziness usually appear at the start of treatment but disappear spontaneously as therapy progresses. Some have also reported nausea, vomiting, headache, seizures, hives, rash. symptoms of central nervous stimulation such as arousal, irritability, insomnia and nervousness have been observed mainly in children.

Compliance with the instructions contained in the package leaflet reduces the risk of undesirable effects. If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet, please tell your doctor or pharmacist.

Expiry and Retention

Expiry: see the expiry date printed on the package.

The expiry date indicated refers to the product in intact packaging, correctly stored.

Warning: do not use the medicine after the expiry date shown on the package.

storage

Store below 25 ° C.

Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. This will help protect the environment.

KEEP THE MEDICINAL PRODUCT OUT OF THE REACH AND SIGHT OF CHILDREN

Composition and pharmaceutical form

COMPOSITION

1 tablet contains:

Active ingredient: ketotifen fumarate acid 2.75 mg (equal to 2 mg of base).

Excipients: magnesium stearate, ethylcellulose, povidone, maize starch, glyceryl palmite stearate, lactose monohydrate, hypromellose, titanium dioxide, polyethylene glycol 6000, talc, anhydrous colloidal silica, yellow iron oxide pigment.

PHARMACEUTICAL FORM AND CONTENT

Prolonged-release tablets: blister packs of 15 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.

More information about Zaditen can be found in the "Summary of Characteristics" tab. 01.0 NAME OF THE MEDICINAL PRODUCT 02.0 QUALITATIVE AND QUANTITATIVE COMPOSITION 03.0 PHARMACEUTICAL FORM 04.0 CLINICAL PARTICULARS 04.1 Therapeutic indications 04.2 Posology and method of administration 04.3 Contraindications 04.4 Special warnings and appropriate precautions for use 04.5 Interactions with other medicinal products and other forms of interaction 04.6 Pregnancy and lactation 04.7 Effects on ability to drive and use machines 04.8 Undesirable effects 04.9 Overdose 05.0 PHARMACOLOGICAL PROPERTIES 05.1 Pharmacodynamic properties 05.2 Pharmacokinetic properties 05.3 Preclinical safety data 06.0 PHARMACEUTICAL PARTICULARS 06.1 Excipients 06.2 Incompatibilities 06.3 Shelf life 06.4 Special precautions for storage 06.5 Nature of the immediate packaging and contents of the package 06.6 Instructions for use and handling 07.0 MARKETING AUTHORIZATION HOLDER 08.0 MARKETING AUTHORIZATION NUMBER 09 .0 DATE OF FIRST AUTHORIZATION OR RENEWAL OF THE AUTHORIZATION 10.0 DATE OF REVISION OF THE TEXT 11.0 FOR RADIO DRUGS, COMPLETE DATA ON INTERNAL RADIATION DOSIMETRY 12.0 FOR RADIO DRUGS, FURTHER DETAILED INSTRUCTIONS AND QUALITY CONTROLS

01.0 NAME OF THE MEDICINAL PRODUCT

ZADITEN TABLETS

02.0 QUALITATIVE AND QUANTITATIVE COMPOSITION

1 tablet contains:

Active principle:

ketotifen acid fumarate 2.75 mg

(equal to 2 mg of base)

Excipients: Lactose

For the full list of excipients see section 6.1

03.0 PHARMACEUTICAL FORM

Prolonged-release tablets.

04.0 CLINICAL INFORMATION

04.1 Therapeutic indications

Symptomatic treatment of allergic rhinitis


04.2 Posology and method of administration

Adults:

2 mg once a day, preferably in the evening; if necessary, 2 mg twice daily (morning and evening, 12 hour interval).

Childi over 3 years old:

2 mg once a day, preferably in the evening.

ZADITEN 2 mg prolonged-release tablets should be swallowed whole.


04.3 Contraindications

Known hypersensitivity to ketotifen or to any of the excipients (see List of excipients); epilepsy; patients being treated with oral antidiabetics; breastfeeding.


04.4 Special warnings and appropriate precautions for use

Ketotifen does not prevent or cure acute asthma attacks.

Medicines already in use for the treatment of asthma symptoms and its prevention must in no way be stopped suddenly if long-term treatment with Zaditen is started. This is especially true when the treatment is based on cortisone drugs. as steroid-dependent patients may be affected by adrenocortical insufficiency; in this case it may take up to a year for the recovery of a normal pituitary-adrenal stress response.

Thrombocytopenia may occur in patients taking Zaditen at the same time as oral antidiabetics. Concomitant administration of these drugs is therefore to be avoided.

Seizures have been reported very rarely during therapy with Zaditen. As Zaditen may lower the seizure threshold, it should be used carefully in patients with a history of epilepsy.

Monitor for signs of severe sleepiness. The onset of somnolence, present mainly in the first days of therapy, may impair some practical skills, for example driving or working with machines (see also section 4.7 Effects on the ability to drive and use machines).

The use of alcoholic beverages and central nervous system depressants (eg sedatives-hypnotics, other antihistamines) is not recommended.

The prolonged-release coated tablets contain lactose. This medicine is not recommended for use in patients with rare hereditary conditions such as lactose intolerance, severe lactase deficiency or glucose-galactose malabsorption.

In case of decreased attention due to the sedative effect of Zaditen, the dose will have to be reduced.


04.5 Interactions with other medicinal products and other forms of interaction

Zaditen may enhance the effects of central nervous system depressants, antihistamines, anticoagulants and alcohol.

Co-administration of oral antidiabetics and Zaditen should be avoided as thrombocytopenia may occur (see section 4.4, Warnings and special precautions for use)

Ketotifen amplifies the effects of any co-administered bronchodilators, whose frequency of use must be suitably reduced.


04.6 Pregnancy and breastfeeding

Pregnancy

Although no effects on pregnancy or peri- and postnatal development were observed in animals at maternal tolerated dosage levels, the safety of ketotifen in human pregnancy has not been established. Zaditen should therefore only be given to pregnant women if conditions dictate it.

Feeding time

Ketotifen is excreted in the breast milk of rats. Since it is also supposed to be excreted in humans, mothers treated with Zaditen should not breastfeed.


04.7 Effects on ability to drive and use machines

In the first days of therapy with Zaditen the patient's ability to react may be reduced; therefore, caution is required when driving vehicles or using machines.


04.8 Undesirable effects

Adverse reactions are listed in Table 1 in order of frequency (most frequent first) and according to the following characteristics: very common (≥ 1/10); common (≥ 1/100,

Table 1

Infections and Infestations

Uncommon: Cystitis

Disorders of the immune system

Very rare: Erythema multiforme, Stevens-Johnson syndrome, Severe skin reaction

Diseases of metabolism and nutrition

Rare: Weight gain

Psychiatric diseases

Common: State of excitement, irritability, insomnia, nervousness

Diseases of the nervous system

Uncommon: Vertigo

Rare: Sedation

Gastrointestinal affections

Uncommon: Dry mouth

Hepatobiliary affections

Very rare: Hepatitis, Increased liver enzymes

Somnolence, sedation, dry mouth and dizziness usually appear at the start of treatment but disappear spontaneously as therapy progresses. Some have also reported nausea, vomiting, headache, convulsions, hives, rash.

Symptoms of central nervous stimulation, such as arousal, irritability, insomnia and nervousness, have been observed mainly in children.


04.9 Overdose

Among the major symptoms of acute overdose we find: drowsiness which can lead to severe sedation; dizziness, confusion and disorientation; bradycardia or tachycardia and hypotension; hyperexcitability or convulsions especially in children; wheezing or respiratory depression; reversible coma. Treatment is symptomatic. Emesis is not recommended due to the risk of seizures. If the drug has been taken recently, stomach emptying may be considered, gastric lavage and the administration of activated charcoal may be considered.

Symptomatic treatment and monitoring of the cardiovascular system are recommended if necessary; if excitation or convulsions are present, benzodiazepines or short-acting barbiturates may be administered. Zaditen is not eliminated by dialysis.

05.0 PHARMACOLOGICAL PROPERTIES

05.1 Pharmacodynamic properties

Pharmacotherapeutic group: antiallergics, antihistamines - ATC code: R06AX17.

ZADITEN 2 mg prolonged-release tablets is an antihistamine that uncompetitively inhibits histamine H1 receptors. ZADITEN 2 mg prolonged-release tablets also has a stabilizing activity on mast cells and inhibiting the release of chemical mediators from mast cells involved in hypersensitivity reactions. It decreases the activation of eosinophils and their flow into the inflammation site.


05.2 "Pharmacokinetic properties

After oral administration the absorption of ketotifen is practically complete. However, its bioavailability is approximately 50% due to a hepatic first pass effect. The bioavailability of the drug is not affected by the presence of food.

The maximum plasma concentration (Cmax) of ketotifen is reached in the adult after 2-4 hours if administered in capsules, in a shorter time (around 2 hours) if administered as a syrup. In the child the peak of maximum concentration is reached in 1 -2 hours Administered in prolonged-release tablets the peak of maximum concentration is reached after 3-6 hours.

The onset of the prophylactic therapeutic effect varies from 4 to 12 weeks. The plasma protein binding is 75%.

The elimination of ketotifen is biphasic, with a short half-life of 3-5 hours and a prolonged half-life of about 21 hours. Ketotifen is metabolized by the liver with glucuroconjugation processes (the main inactive metabolite is ketotifen-N-glucuronide) and demethylation ( active metabolite nor-ketotifen). 60-70% of the dose is eliminated via the kidney, predominantly as inactive metabolites, within 48 hours. 30 to 40% of the dose is eliminated in the faeces. 3.61 L / hr / kg. In children the metabolism mechanism is identical to that of adults, however they have a higher clearance and therefore the dosage of ketotifen recommended for children over three years of age is the same as that proposed for the adults.


05.3 Preclinical safety data

Acute toxicity

In acute toxicity studies of ketotifen in mice, rats and rabbits the LD50 for oral administration was> 300 mg / kg and ranged from 5 to 20 mg / kg after iv administration. Adverse events induced following overdose were dyspnoea and motor arousal followed by spasms and drowsiness. Toxic symptoms occur rapidly and disappear within hours; there is no evidence of cumulative or delayed effects.

Mutagenesis

Ketotifen and / or its metabolites were found to have no genotoxic potential in vitro, as demonstrated in genetic mutation tests and salmonella typhimurium, Chinese hamster cell chromosomal aberration test V79, or DNA repair test in cultures. rat hepatocytes. No clastogenic activity was observed in vivo (cytogenic analysis of bone marrow cells in Chinese hamster, micronucleus test in mice). Similarly, no mutagenic effects were shown in male mouse germ cells in the dominant lethal test.

Carcinogenesis

In rats treated continuously with the diet for 24 months, the maximum tolerated dose of 71 mg / kg / day of ketotifen did not demonstrate any carcinogenic potential. No evidence of tumorigenic effects occurred in the mice treated up to 88 mg / kg for 74 weeks.

Reproductive toxicity

No embryotoxic potential due to ketotifen occurred in the rat or rabbit. In the male rat treated for 10 weeks (duration greater than a complete spermatogenic cycle) prior to mating, the tolerated dose of 10 mg / kg / day did not affect fertility.

In female rats, fertility, prenatal development, pregnancy, lactation of the litter were not affected by treatment with ketotifen at oral doses up to 50 mg / kg / day, although non-specific toxicity for pregnant females was observed. at doses> 10 mg / kg. Only at these doses were decreases in birth survival and weight gain during the early days of postnatal development at the highest dose of 50 mg / kg / day.

No adverse reactions attributable to treatment were observed in the perinatal phase.

06.0 PHARMACEUTICAL INFORMATION

06.1 Excipients

Magnesium stearate, ethylcellulose, povidone, corn starch, glyceryl palmito stearate, lactose monohydrate, hypromellose, titanium dioxide, polyethylene glycol 6000, talc, colloidal anhydrous silica, yellow iron oxide pigment.


06.2 Incompatibility

None.


06.3 Period of validity

3 years


06.4 Special precautions for storage

Store below 25 ° C.


06.5 Nature of the immediate packaging and contents of the package

15 prolonged-release tablets of 2 mg for oral use


06.6 Instructions for use and handling

No special instructions.

07.0 MARKETING AUTHORIZATION HOLDER

DEFIANTE PHARMACEUTICAL SA

Rua dos Ferreiros, 260 - Funchal (Portugal)

Dealer for Italy

BIOFUTURA PHARMA S.p.A.

Via Pontina km 30,400 - 00040 Pomezia (Rome)

08.0 MARKETING AUTHORIZATION NUMBER

A.I.C. n. 024574042

09.0 DATE OF FIRST AUTHORIZATION OR RENEWAL OF THE AUTHORIZATION

First authorization: 16.03.1993

Renewal: 01.06.2010

10.0 DATE OF REVISION OF THE TEXT

December 2010

11.0 FOR RADIO DRUGS, COMPLETE DATA ON THE INTERNAL RADIATION DOSIMETRY

12.0 FOR RADIO DRUGS, FURTHER DETAILED INSTRUCTIONS ON EXEMPORARY PREPARATION AND QUALITY CONTROL

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