ZADITEN

1 Dosing Considerations Concomitant Therapy: Zaditen is for use as add-on maintenance treatment for mild atopic asthma. Existing asthma therapy should be maintained. A progressive reduction in dosage of other asthma therapy, where clinically indicated, should be attempted only after 6-12 weeks of Zaditen therapy.

Zaditen is for maintenance treatment. Patients should be made aware that for optimum benefit, it should be used on a continuous basis. Zaditen should not be used more often than recommended or at higher doses than recommended. Several weeks of Zaditen therapy may be necessary before the therapeutic effect becomes clinically evident.

Full clinical effectiveness is generally reached after 10 weeks of treatment. It is therefore recommended that for patients not adequately responding within a few weeks, treatment with Zaditen should be maintained for a minimum of 2 to 3 months.

If it is necessary to withdraw Zaditen, this should be done progressively over a period of 2 to 4 weeks as symptoms of asthma may recur. Zaditen <Ketotifen Tablets> Page 5 of 21 Patients should be informed that Zaditen should not be used to treat acute symptoms of asthma.

g. salbutamol) to relieve acute symptoms such as shortness of breath. Patients should be advised to have this available for use at all times. 2 Recommended Dose and Dosage Adjustment Children 5 to < 18 years of age In children 5 years of age and older, Zaditen should be given at a dose of 1 tablet (1 mg) twice daily, once in the morning and once in the evening.

To minimize the initial sedation with Zaditen, a slow increase in dosage is recommended during the first week of treatment commencing with one half the daily recommended dosage given in 2 divided doses or in a single dose given in the evening, followed within 5 days, by an increase to the full therapeutic dose.

4 Administration For oral use. Patients should be instructed to swallow the tablets whole. 5 Missed Dose If a dose is missed, it should be taken as soon as possible. If it is almost time for the next dose, the missed dose should be skipped and the next dose taken at the usual time.

A double dose should not be taken.

1 Adverse Reaction Overview The safety of Zaditen is based on data from patients 5 to 17 years of age in a double- blind, placebo-controlled 30 week trial. The most common adverse reactions reported with Zaditen treated patients were weight gain, respiratory infections and rash.

2 Clinical Trial Adverse Reactions Clinical trials are conducted under very specific conditions. The adverse reaction rates observed in the clinical trials; therefore, may not reflect the rates observed in practice and should not be compared to the rates in the clinical trials of another drug.

Adverse reaction information from clinical trials may be useful in identifying and approximating rates of adverse drug reactions in real-world use. 1 Clinical trial adverse reactions - pediatrics The following adverse reactions were reported in a Canadian multicentre double-blind, placebo-controlled 30 week trial involving 196 asthmatic children aged 5 to 17 years.

3 0 0 There was a relatively low incidence of adverse reactions reported. These were similar in both the Zaditen and placebo treated groups of patients. 2 Drug Interactions Overview). Occasional, isolated, instances of elevated liver enzymes levels have been seen during clinical trials.

No definite relationship to ketotifen fumarate therapy has been established. 5 Post-Market Adverse Reactions Sedation and, rarely, dry mouth or slight dizziness may occur at the beginning of treatment, but usually disappear spontaneously with continued medication.

Occasionally, symptoms of CNS stimulation, such as excitation, irritability, insomnia and nervousness have been observed, particularly in children. Weight gain has also been reported. Cystitis has been rarely described in association with Zaditen.

Very rarely Zaditen may cause an increase in liver enzymes and hepatitis. Isolated cases of severe skin reactions (erythema multiforme, Stevens Johnson syndrome), have been reported, the occurrence being approximately 1 case in 2 million patients exposed to Zaditen.

, as rescue therapy for the treatment of acute episodes of bronchospasm). , salbutamol) to relieve acute symptoms such as shortness of breath, and advised to have this available for use at all times. For add-on therapy Zaditen should not be used as monotherapy.

Symptomatic and maintenance asthma therapy (xanthine derivatives, β2-adrenergic agonists, sodium cromoglycate, corticosteroids) already in use should be continued and should not be reduced immediately when treatment with Zaditen is initiated.

Zaditen is indicated for children with mild asthma who should be taking low dose asthma medications, therefore reduction in dose of other asthma treatments may not be possible. Driving and Operating Machinery Drowsiness may occur in the early stages of therapy, therefore patients engaging in activities requiring rapid and precise responses should be cautioned.

Patients should exercise caution when driving or operating a vehicle or potentially dangerous machinery Immune Hypersensitivity reactions have been reported with ketotifen. Neurologic Convulsions have been reported very rarely during Zaditen therapy.

As Zaditen may lower the seizure threshold it should be used with caution in patients with a history o f epilepsy or seizures. In particular, young children may be more susceptible to developing new seizures during treatment ketotifen.

Zaditen should be discontinued in patients who experience a seizure while on treatment. 1 Pregnant Women Although ketotifen was without effect on pregnancy and on peri- and post-natal development at dose levels which were tolerated by the mother animals, its safety in human pregnancy has not been established.

Zaditen should therefore be given to pregnant women only if the benefits outweigh the risks. 2 Breast-feeding It is not known whether ketotifen is excreted in human breast milk. However, ketotifen is excreted in rat milk. It is assumed that this drug is also excreted in human breast milk , and therefore mothers taking Zaditen should not breast-feed.

Zaditen is contraindicated in patients who are hypersensitive to this drug or to any ingredient in the formulation, including any non-medicinal ingredient, or component of the container. For a complete listing, see 6 DOSAGE FORMS, STRENGTHS, COMPOSITION AND PACKAGING.