Zaditor (Ketotifen Fumarate Ophthalmic) - Description and Clinical Pharmacology

ZADITOR ™

Ketotifen Fumarate

Ophthalmic Solution, 0.025%

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)-4 H -benzo[4,5]cyclohepta[1,2- b ] thiophen-10(9 H)-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.

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.