PART I: HEALTH PROFESSIONAL INFORMATION 3

SUMMARY PRODUCT INFORMATION 3 INDICATIONS AND CLINICAL USE 3 CONTRAINDICATIONS 3 WARNINGS AND PRECAUTIONS 3 ADVERSE REACTIONS 4 DRUG INTERACTIONS 4 DOSAGE AND ADMINISTRATION 4 OVERDOSAGE 5 ACTION AND CLINICAL PHARMACOLOGY 5 STORAGE AND STABILITY 5 DOSAGE FORMS, COMPOSITION AND PACKAGING 5

PART II: SCIENTIFIC INFORMATION 7

PHARMACEUTICAL INFORMATION 7 DETAILED PHARMACOLOGY 8 TOXICOLOGY 9 REFERENCES 11

PART III: CONSUMER INFORMATION. 12

ZADITOR *

Ketotifen Fumarate Ophthalmic Solution

Route of Administration Dosage Form / Strength Clinically Relevant Nonmedicinal Ingredients
Topical (instillation) Ophthalmic Solution 0.025% as ketotifen Multi dose container: Preservative benzalkonium chloride 0.01% For a complete listing see Dosage Forms, Composition and Packaging section.

PART I: HEALTH PROFESSIONAL INFORMATION SUMMARY PRODUCT INFORMATION

INDICATIONS AND CLINICAL USE

ZADITOR * (ketotifen fumarate ophthalmic solution) is indicated for: treatment of allergic conjunctivitis.

CONTRAINDICATIONS

Patients who are hypersensitive to this drug or to any ingredient in the formulation or component of the container. For a complete listing, see the Dosage Forms, Composition and Packaging section of the product monograph.

WARNINGS AND PRECAUTIONS

General

For topical use only. Not for injection or oral use.

Multi Dose Container:

As with all ophthalmic preparations containing benzalkonium chloride, patients are advised not to instill ZADITOR * (ketotifen fumarate ophthalmic solution) while wearing soft (hydrophilic) contact lenses. Wearers of soft contact lenses should be instructed to remove lenses prior to instillation of drops and to wait at least ten minutes after instilling ZADITOR(tm) before they insert their contact lenses.

To prevent contaminating the dropper tip and solution, care should be taken not to touch the eyelids or surrounding areas with the dropper tip of the bottle. Keep the bottle tightly closed when not in use.

Special Populations

Pregnant Women:

There are no clinical trials on the use of ZADITOR * (ketotifen fumarate ophthalmic solution) in pregnant or nursing women, therefore, ZADITOR * should not be used during pregnancy, except if the benefit justifies the potential risk to the foetus.

Pediatrics (> 3 years of age)

: ZADITOR * is indicated for use in pediatric patients over the age of 3 years.

ADVERSE REACTIONS

Adverse Drug Reaction Overview

In controlled clinical studies with ZADITOR * (ketotifen fumarate ophthalmic solution), conjunctival injection was the most common ocular adverse reaction related to therapy, with a reported incidence of 7.0%. Headache was the most common non-ocular adverse reaction related to therapy, with a reported incidence of 1.5%. The occurrence of these side effects were generally mild and did not result in discontinuation or interruption of trial medication. The following ocular adverse reactions related to therapy were reported at an incidence of less than 3%. Itching, dry eyes, burning or stinging, eyelid disorder and discharge.

DRUG INTERACTIONS

Overview

If ZADITOR * (ketotifen fumarate ophthalmic solution) is used concomitantly with other eye medications, patients should be advised to wait at least 5 minutes between the medications.

DOSAGE AND ADMINISTRATION

Dosing Considerations

Single dose containers:

The contents remain sterile until the original closure is broken. Single dose containers must be discarded after use.

Recommended Dose and Dosage Adjustment

The recommended dose is one drop in the affected eye(s) every 8 to 12 hours.

OVERDOSAGE

Oral ingestion of the contents of a 5 mL bottle would be equivalent to 1.25 mg of ketotifen fumarate. Clinical results have shown no serious signs or symptoms after the ingestion of up to 20 mg of ketotifen fumarate.

ACTION AND CLINICAL PHARMACOLOGY

Mechanism of Action

Ketotifen is a fast acting non-competitive histamine antagonist (H1-receptor). In addition, ketotifen inhibits the release of mediators from mast cells involved in hypersensitivity reactions. Decreased chemotaxis and activation of eosinophils has also been demonstrated. Additionally, ketotifen attenuates the effects of PAF and inhibits cAMP phosphodiesterase. In human conjunctival allergen challenge studies, ZADITOR * (ketotifen fumarate ophthalmic solution) was significantly more effective than placebo in preventing ocular itching and redness associated with allergic conjunctivitis. The effect was seen within minutes after administration and lasted up to 12 hours.

Pharmacodynamics

In human conjunctival allergen challenge studies, ZADITOR * was significantly more effective than placebo in preventing ocular itching and redness associated with allergic conjunctivitis. The effect was seen within minutes after administration and lasted up to 12 hours. In a placebo-controlled clinical study designed to evaluate safety, ZADITOR *, administered four times a day for 6 weeks, was shown to be safe and well-tolerated in subjects aged 3 years and older.

STORAGE AND STABILITY

Multi dose containers

: Store between 4degC and 25degC.

Single dose containers

: Store between 4degC and 25degC. After opening a blister, unused single dose containers may be stored for 4 weeks. Single dose containers may be stored outside the blister in the outer carton for 3 months.

DOSAGE FORMS, COMPOSITION AND PACKAGING

Multi dose containers

: Each mL of ZADITOR * (ketotifen fumarate ophthalmic solution) contains:

Active:

0.345 mg ketotifen fumarate equivalent to 0.25 mg ketotifen.

Preservative:

benzalkonium chloride 0.01%

Inactives:

glycerol, hydrochloric acid/sodium hydroxide and purified water.

Single dose containers

: Each mL of ZADITOR *(ketotifen fumarate ophthalmic solution) contains:

Active:

0.345 mg ketotifen fumarate equivalent to 0.25 mg ketotifen.

Inactives:

glycerol, sodium hydroxide and water for injection.

Packaging :

Multi dose containers

: ZADITOR * is available in multi dose in white plastic bottles with controlled dropper tips containing 5 mL of clear solution.

Single dose containers:

ZADITOR * is available in preservative-free single dose, transparent containers containing 0.4 mL of clear solution. Blocks of 5 single dose containers are each packed in a blister. Carton boxes of 30 single dose containers are available.