Zaditor® is an antihistamine eye drop to relieve itchy eyes due to allergens.

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&reade; 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.

Last updated on RxList: 5/15/2008

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

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

Children under 3 years of age: Consult a doctor.

ZADITOR comes in a 5 ml bottle that contains a 30-day supply if dosed as directed.

Storage

Store at 4°- 25° C (39°- 77° F).

Novartis Pharmaceuticals Corporation
One Health Plaza
East Hanover, New Jersey 07936-1080

Last updated on RxList: 5/15/2008

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.

No information provided.

Last updated on RxList: 5/15/2008

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

See PATIENT INFORMATION section.

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 ³10 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

Pregnancy Category C

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.

Last updated on RxList: 5/15/2008

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

Last updated on RxList: 5/15/2008

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.

Last updated on RxList: 5/15/2008

What is Zaditor?
Zaditor (ketotifen fumarate ophthalmic solution 0.025%) is an over-the-counter (OTC) antihistamine eye drop that relieves itchy eyes due to allergens. It's the first OTC eye drop strong enough to last up to 12 hours with just one drop. Previously available only with a prescription, Zaditor is now available OTC in original prescription strength.

What is the difference between Zaditor and leading OTC antihistamine eye drops?
With Zaditor, you can expect fast, effective relief with just one drop that lasts up to 12 hours, whereas the leading OTC eye drops only provide relief for up to 4-6 hours. Some OTC itchy eye products also contain redness relievers (vasoconstrictors) that through repeated use can actually cause your eyes to become even redder after the effect of the vasoconstrictor wears off. This is called the "rebound effect." Zaditor works differently from these types of products. It stops the itch at the source by also blocking histamines (a chemical made by the body during an allergic reaction) that causes itchy eyes but does not directly constrict blood vessels. With Zaditor, you don't have to worry about worsening your symptoms as a result of the "rebound effect."

Why did Novartis Ophthalmics apply to the FDA to change Zaditor from prescription to OTC?
Since its introduction in the U.S. in 1999, Zaditor has been safely used by millions for the temporary prevention of itchy eyes due to allergic conjunctivitis. By making Zaditor available OTC, itchy eye sufferers can experience fast, long-lasting relief from itchy eyes without a prescription.

Is OTC Zaditor the same strength as original prescription-strength Zaditor?
Yes. You can now benefit from the same prescription-strength Zaditor without a prescription.

How safe is Zaditor?
The FDA has determined that Zaditor is safe for OTC use based on the long-term use of the drug, as well as the controlled clinical studies that supported the original prescription-strength formula.

Is Zaditor safe for use in children?
Yes. Zaditor is safe for children as young as 3 years old.

Can Zaditor be used in both eyes?
Zaditor should only be applied to the eye or eyes that are affected.

How is Zaditor administered?
The recommended dose is one drop in the affected eye(s) twice daily.

Can Zaditor be used with contact lenses?
Yes. However, contact lenses should be removed prior to applying Zaditor and not reinserted for at least 10 minutes following application.

Does Zaditor treat seasonal allergic conjunctivitis?
Zaditor relieves itchy eyes caused by seasonal allergic conjunctivitis.

Does Zaditor treat perennial allergic conjunctivitis?
Zaditor relieves itchy eyes caused by perennial allergic conjunctivitis.

Does Zaditor treat pink eye?
Zaditor relieves the symptoms of allergic conjunctivitis, which is a type of pink eye. Other causes of pink eye include infectious (viral, bacterial and fungal), inflammatory (rheumatoid arthritis, systemic lupus erythematosus, etc) and toxic (chemical and other irritants). Always consult your health-care professional for proper diagnosis and treatment.

How much does Zaditor cost?
Suggested retail price for a 30-day supply is $14.99.

Is Zaditor covered by insurance?
Typically, OTC medications are not covered by health insurance.

What are some of the causes of itchy eyes?
Itchy eyes can be caused by seasonal or perennial allergens such as pollen, ragweed, mold, dust, animal hair and pet dander. Worsening or prolongation of symptoms should be seen by a medical professional.

When and where will Zaditor be available OTC?
Zaditor has been available OTC in retail stores since January 2007.

What is the preservative in Zaditor?
The preservative in Zaditor is benzalkonium chloride.

How should Zaditor be stored?
Zaditor should be stored at temperatures between 39° and 77° F.

What size is the Zaditor bottle?
Zaditor comes in a 5 ml bottle that contains a 30-day supply if dosed as directed.

Last updated on RxList: 5/15/2008

IMPORTANT NOTE: This is a summary and does not contain all possible information about this product. For complete information about this product or your specific health needs, ask your health care professional. Always seek the advice of your health care professional if you have any questions about this product or your medical condition. This information is not intended as individual medical advice and does not substitute for the knowledge and judgment of your health care professional. This information does not contain any assurances that this product is safe, effective, or appropriate for you.

KETOTIFEN - OPHTHALMIC

(kee-TOE-tih-fen)

COMMON BRAND NAME(S): Zaditor

USES: This medication is used to prevent and treat itching of the eyes caused by allergies (allergic/seasonal conjunctivitis). Ketotifen is an antihistamine for the eye that treats allergic symptoms by blocking a certain natural substance (histamine). It is also a mast cell stabilizer that prevents allergic reactions by reducing the release of natural substances that cause an allergic reaction.

HOW TO USE: If you are using the over-the-counter product, read all directions on the product package before using this medication. If your doctor has prescribed this medication, use it exactly as directed.

Apply 1 drop to the affected eye(s), usually twice a day (every 8 to 12 hours) or as directed by the package instructions or your doctor.

Dosage is based on your medical condition and response to treatment.

To apply eye drops, wash your hands first. To avoid contamination, do not touch the dropper tip or let it touch your eye or any other surface.

Ask your doctor if you can wear contact lenses while you are being treated with this medication. If your doctor says you may continue wearing them, remove them before using the eye drops, and wait at least 10 minutes after each dose before putting in your lenses. Do not use this medication to treat irritation from contact lens wear. Consult your doctor about the use of contact lenses when the eyes are red or irritated.

Tilt your head back, look upward, and pull down the lower eyelid to make a pouch. Hold the dropper directly over your eye and apply 1 drop in the lower eyelid. Look downward and gently close your eyes for 1 to 2 minutes. Place one finger at the corner of your eye (near the nose) and apply gentle pressure. This will prevent the medication from draining out. Try not to blink and do not rub your eye.

Do not rinse the dropper. Replace the dropper cap after each use, and keep the bottle tightly closed.

If you are using another kind of eye medication (drops or ointment), wait at least 5 minutes before applying it. Apply eye drops before eye ointments to allow the eye drops to enter the eye.

If your doctor has prescribed this medication, use it regularly in order to get the most benefit from it. To help you remember, use it at the same times each day. Continue to use this medication as prescribed until pollen season is over or you are no longer exposed to the allergic substance, even when allergic symptoms disappear or improve.

If your condition persists or worsens, if you develop new symptoms, or if you think you have a serious medical problem, seek immediate medical attention. If you are treating yourself with nonprescription ketotifen, consult your doctor if your itching worsens or lasts more than 72 hours. You may need a different medication.

SIDE EFFECTS: Burning/stinging/irritation of the eye, headache, stuffy/runny nose, bad taste in your mouth, and increased sensitivity to light may occur. If any of these effects persist or worsen, tell your doctor or pharmacist promptly.

If your doctor has directed you to use this medication, remember that he or she has judged that the benefit to you is greater than the risk of side effects. Many people using this medication do not have serious side effects.

Tell your doctor immediately if any of these unlikely but serious side effects occur: dry eyes, eye pain, increased redness/swelling of the eye, vision problems.

A very serious allergic reaction to this drug is rare. However, seek immediate medical attention if you notice any symptoms of a serious allergic reaction, including: rash, itching, swelling, severe dizziness, trouble breathing.

This is not a complete list of possible side effects. If you notice other effects not listed above, contact your doctor or pharmacist.

Contact your doctor for medical advice about side effects. The following numbers do not provide medical advice, but in the US you may report side effects to the Food and Drug Administration (FDA) at 1-800-FDA-1088. In Canada, you may call Health Canada at 1-866-234-2345.

PRECAUTIONS: Before using ketotifen, tell your doctor or pharmacist if you are allergic to it; or to the preservative benzalkonium chloride (if using the multi-dose container); or if you have any other allergies.

Before using this medication, tell your doctor or pharmacist your medical history, especially of: eye problems (e.g., glaucoma).

After you apply this drug, your vision may become temporarily blurred. Use caution while driving, using machinery, or doing any other activity that requires clear vision.

Do not use this medication in children younger than 3 years unless directed by the doctor.

During pregnancy, this medication should be used only when clearly needed. Discuss the risks and benefits with your doctor.

It is not known whether this drug passes into breast milk. Consult your doctor before breast-feeding.

DRUG INTERACTIONS: If this drug has been prescribed, your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them. Do not start, stop, or change the dosage of any medicine before checking with your doctor or pharmacist first.

Before using this medication, tell your doctor or pharmacist of all prescription and nonprescription/herbal products you may use.

Keep a list of all your medications with you, and share the list with your doctor and pharmacist.

OVERDOSE: This medicine may be harmful if swallowed. If swallowing or overdose is suspected, contact your local poison control center or emergency room immediately. US residents can call the US National Poison Hotline at 1-800-222-1222. Canada residents can call a provincial poison control center.

NOTES: Do not share this medication with others.

Avoid allergens (e.g., pollen, animal dander) and other triggering factors (e.g., irritants). Cold compresses and lubricating eye drops may decrease eye irritation.

MISSED DOSE: If you are using this medication on a regular schedule and miss a dose, use it as soon as you remember. If it is near the time of the next dose, skip the missed dose and resume your usual dosing schedule. Do not double the dose to catch up.

STORAGE: Store between 39-77 degrees F (4-25 degrees C) away from light and moisture. If you are using the single-dose container, discard it after use. Discard unused single-dose containers 4 weeks after you first open the blister pack (or 3 months after opening if you store them in the original carton box). Do not store in the bathroom. Keep all medicines away from children and pets.

Do not flush medications down the toilet or pour them into a drain unless instructed to do so. Properly discard this product when it is expired or no longer needed. Consult your pharmacist or local waste disposal company for more details about how to safely discard your product.

Information last revised July 2008 Copyright(c) 2008 First DataBank, Inc.