Zaditor

Zaditor is an over-the-counter (OTC) eyedrop used to temporarily relieve itchy eyes due to pollen, ragweed, grass, animal hair and dander. Zaditor belongs to a group of drugs called antihistamines. It works by blocking histamine receptors and decreasing the release of histamine from cells in the body.

Zaditor comes as an eyedrop that is applied twice daily.

Side effects may include red eyes, runny nose and headache.

• Adults and children 3 years of age and older: Put 1 drop in the affected eye(s) twice daily, every 8 to 12 hours, no more than twice per day.
• Children under 3 years of age: Consult a doctor.

If swallowed, get medical help or contact a Poison Control Center right away.

Ketotifen is an antihistamine that reduces the effects of natural chemical histamine in the body. Histamine can produce symptoms of sneezing, itching, watery eyes, and runny nose.

Ketotifen ophthalmic (for use in the eyes) is used to treat itching of the eyes caused by allergy to dust, pollen, animals, or other allergens.

Ketotifen ophthalmic may also be used for purposes not listed in this medication guide.

Get emergency medical help if you have signs of an allergic reaction: hives; difficult breathing; swelling of your face, lips, tongue, or throat.

Stop using ketotifen ophthalmic and call your doctor at once if you have:

• redness, drainage, eyelid swelling, or other signs of infection;

• eye pain;

• vision changes; or

• severe itching of the eyes worse than before using the medication.

Common side effects may include:

• mild burning, stinging, or eye irritation;

• dryness of the eyes; or

• increased sensitivity to light.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Storage

Ophthalmic

4–25°C.6 7

Do not use if solution changes color or becomes cloudy.6 7

• Importance of learning and adhering to proper administration techniques to avoid contamination of the product.6 7

• Importance of delaying insertion of contact lenses for at least 10 minutes after ketotifen instillation to prevent absorption of benzalkonium chloride by contact lenses.1 6 7

• Not indicated for contact lens-related irritation.6 7

• Importance of reporting new-onset eye pain or discomfort, visual disturbances, eye redness, worsening of itching, or itching lasting >72 hours.6 7

• Importance of seeking quick medical attention if preparation is ingested orally.6 7

• Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.1

• Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as any other concomitant illnesses.6 7

• Importance of informing patient of other important precautionary information.6 7 (See Cautions.)

Ketotifen ophthalmic (eye) solution is used to temporarily prevent itching of the eye caused by a condition known as allergic conjunctivitis. It works by acting on certain cells, called mast cells, to prevent them from releasing substances that cause the allergic reaction.

This medicine is available both over-the-counter (OTC) and with your doctor's prescription.

• If you have an allergy to ketotifen or any other part of Zaditor (ketotifen (ophthalmic)).
• If you are allergic to any drugs like this one, any other drugs, foods, or other substances. Tell your doctor about the allergy and what signs you had, like rash; hives; itching; shortness of breath; wheezing; cough; swelling of face, lips, tongue, or throat; or any other signs.

This medicine may interact with other drugs or health problems.

Tell your doctor and pharmacist about all of your drugs (prescription or OTC, natural products, vitamins) and health problems. You must check to make sure that it is safe for you to take this medicine with all of your drugs and health problems. Do not start, stop, or change the dose of any drug without checking with your doctor.

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.

Information for patients

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. Patients should be advised not to wear a contact lens if their eye is red. Zaditor™ should not be used to treat contact lens related irritation. The preservative in Zaditor™, benzalkonium chloride, may be absorbed by soft contact lenses. Patients who wear soft contact lenses and whose eyes are not red, should be instructed to wait at least ten minutes after instilling Zaditor™ before they insert their contact lenses.

Carcinogenesis, Mutagenesis, Impairment of Fertility

Ketotifen fumarate was determined to be non-mutagenic in a battery of in vitro and in vivo mutagenicity assays including: Ames test, in vitro chromosomal aberration test with V79 Chinese hamster cells, in vivo micronucleus assay in mouse, and mouse dominant lethal test.

Treatment of male rats with oral doses of ketotifen ≥ 10 mg/kg/day orally [6,667 times the maximum recommended human ocular dose of 0.0015 mg/kg/day on a mg/kg basis (MRHOD)] for 70 days prior to mating resulted in mortality and a decrease in fertility. Treatment with ketotifen did not impair fertility in female rats receiving up to 50 mg/kg/day of ketotifen orally (33,333 times the MRHOD) for 15 days prior to mating.

Pregnancy

Oral treatment of pregnant rabbits during organogenesis with 45 mg/kg/day of ketotifen (30,000 times the MRHOD) resulted in an increased incidence of retarded ossification of the sternebrae. However, no effects were observed in rabbits treated with up to 15 mg/kg/day (10,000 times the MRHOD). Similar treatment of rats during organogenesis with 100 mg/kg/day of ketotifen (66,667 times the MRHOD) did not reveal any biologically relevant effects.

Oral treatment of pregnant rats (up to 100 mg/kg/day or 66,667 times the MRHOD) and rabbits (up to 45 mg/kg/day or 30,000 times the MRHOD) during organogenesis did not result in any biologically relevant embryofetal toxicity. In the offspring of the rats that received ketotifen orally from day 15 of pregnancy to day 21 post partum at 50 mg/kg/day (33,333 times the MRHOD), a maternally toxic treatment protocol, the incidence of postnatal mortality was slightly increased, and body weight gain during the first four days post partum was slightly decreased.

Nursing Mothers

Ketotifen fumarate has been identified in breast milk in rats following oral administration. It is not known whether topical ocular administration could result in sufficient systemic absorption to produce detectable quantities in breast milk. Nevertheless, caution should be exercised when ketotifen fumarate is administered to a nursing mother.

Pediatric Use

Safety and effectiveness in pediatric patients below the age of 3 years have not been established.

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.