ZADITOR™

Ketotifen Fumarate

Ophthalmic Solution, 0.025%

Zaditor Description

ZADITOR™ is a sterile ophthalmic solution containing ketotifen for topical administration to the eyes. Ketotifen fumarate is a finely crystalline powder with an empirical formula of C23H23NO5S and a molecular weight of 425.50.

Established Name: ketotifen fumarate ophthalmic solution

CHEMICAL NAME

4-(1-Methyl-4-piperidylidene)-4H-benzo[4,5]cyclohepta[1,2-b] thiophen-10(9H)-one hydrogen fumarate

Each mL of ZADITOR™ contains: Active: 0.345 mg ketotifen fumarate equivalent to 0.25 mg ketotifen. Inactives: glycerol, sodium hydroxide/hydrochloric acid (to adjust pH) and purified water.

Preservative: benzalkonium chloride 0.01%. It has a pH of 4.4 to 5.8 and an osmolality of 210-300 mOsm/kg.

Zaditor - Clinical Pharmacology

Ketotifen is a relatively selective, non-competitive histamine antagonist (H1-receptor) and mast cell stabilizer. Ketotifen inhibits the release of mediators from cells involved in hypersensitivity reactions. Decreased chemotaxis and activation of eosinophils has also been demonstrated.

Ketotifen has been shown to have little systemic exposure following topical ocular administration. A study conducted with 15 healthy volunteers dosed bilaterally with ketotifen fumarate ophthalmic solution twice daily for 14 days demonstrated plasma concentrations generally below the quantitation limit of assay (< 20 pg/mL).

In human conjunctival allergen challenge studies, ZADITOR™ was significantly more effective than placebo in preventing ocular itching associated with allergic conjunctivitis. The action of ketotifen occurs rapidly with an effect seen within minutes after administration.

Indications and Usage for Zaditor

ZADITOR™ (ketotifen fumarate ophthalmic solution) is indicated for the temporary prevention of itching of the eye due to allergic conjunctivitis.

Contraindications

ZADITOR™ is contraindicated in persons with a known hypersensitivity to any component of this product.

Warnings

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

Precautions

Adverse Reactions/Side Effects

In controlled clinical studies, conjunctival injection, headaches, and rhinitis were reported at an incidence of 10 to 25%. The occurrence of these side effects was generally mild. Some of these events were similar to the underlying ocular disease being studied.

The following ocular and non-ocular adverse reactions were reported at an incidence of less than 5%:

Ocular: Allergic reactions, burning or stinging, conjunctivitis, discharge, dry eyes, eye pain, eyelid disorder, itching, keratitis, lacrimation disorder, mydriasis, photophobia, and rash.

Non-Ocular: Flu syndrome, pharyngitis.

Overdosage

Oral ingestion of the contents of a 5 mL bottle would be equivalent to 1.725 mg of ketotifen fumarate. Clinical results have shown no serious signs or symptoms after the ingestion of up to 20 mg of ketotifen fumarate.

Zaditor Dosage and Administration

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

How is Zaditor supplied

NDC 58768-102-05 ZADITOR 5 mL is supplied in a white Polypropylene (PP) 7.5 cc container with a PP dropper tip and closure.

NDC 58768-102-99 ZADITOR 1 mL is supplied in a white Low Density Polyethylene (LDPE) 3.0 cc container with a LDPE dropper tip and PP closure.

Storage and Handling

Store at 4º - 25ºC (39º - 77ºF)

Rx Only

Made in Canada by CIBA Vision Sterile Mfg.

for Novartis Ophthalmics

Duluth, GA 30097

October, 2002

I6137-E