Professional Drug Information > Zaditor

Ketotifen (Ophthalmic)

VA CLASSIFICATION
Primary: OP801

Commonly used brand name(s): Zaditor.

Note: For a listing of dosage forms and brand names by country availability, see Dosage Forms section(s).



Category:


Antihistaminic (H₁-receptor), ophthalmic—

mast cell stabilizer, ophthalmic—

antiallergic, ophthalmic—

Indications

Accepted

Conjunctivitis, allergic (prophylaxis)— Ophthalmic ketotifen is indicated for the temporary prevention of itching of the eye due to allergic conjunctivitis.^{01}


Pharmacology/Pharmacokinetics

Physicochemical characteristics:
Molecular weight—
     Ketotifen fumarate: 425.5^{01}
     pH— 4.4 to 5.8^{01}

Mechanism of action/Effect:

Ketotifen is a relatively selective, non-competitive histamine H₁-receptor antagonist and mast cell stabilizer. ^{01} Ketotifen inhibits the release of mediators from cells involved in hypersensitivity reactions. Ketotifen also decreases chemotaxis and activation of eosinophils.^{01}

Onset of action:

Within minutes of application ^{01}.


Precautions to Consider

Mutagenicity

No mutagenicity was demonstrated in the following in vitro and in vivo models: Ames test, chromosomal aberration test with V79 Chinese hamster cells, micronucleus assay in mouse, and mouse dominant lethal test.

Pregnancy/Reproduction
Fertility—
In male rats at oral doses ³ 10 mg/kg per day (6667 times the maximum recommended human ocular dose [MRHOD] of 0.0015 mg/kg per day) for 70 days prior to mating, ketotifen caused mortality and decreased fertility. In female rats at oral doses of 50 mg/kg per day (33,333 times the MRHOD) for 15 days prior to mating, ketotifen did not impair fertility.^{01}

Pregnancy—
Adequate and well-controlled studies in humans have not been done.

Ketotifen caused an increased incidence of retarded ossification of the sternebrae in the offspring of pregnant rabbits that have been given doses of 45 mg/kg per day (30,000 times the MRHOD) during organogenesis. However, no effects were observed in rabbits given doses up to 15 mg/kg per day (10,000 times the MRHOD) or rats treated with up to 100 mg/kg per day (66,667 times the MRHOD).^{01}

Ketotifen caused no biologically relevant embryofetal toxicity in pregnant rats given doses up to 100 mg/kg per day (66,667 times the MRHOD) and rabbits given doses up to 45 mg/kg per day (30,000 times the MRHOD) during organogenesis .

FDA Pregnancy Category C. ^{01}

Postpartum—
In the offspring of the rats that received ketotifen orally from day 15 of pregnancy to day 21 postpartum at a dose of 15 mg/kg per day (33,333 times the MRHOD), the incidence of postnatal mortality was slightly increased, and body weight gain during the first 4 days postpartum was slightly decreased.^{01}

Breast-feeding

It is not known whether ophthalmic ketotifen is absorbed in sufficient quantities to be distributed into human breast milk. However, it has been found in the milk of nursing rats following oral administration. ^{01}

Pediatrics

Appropriate studies on the relationship of age to the effects of ketotifen have not been performed in the pediatric population in children younger than 3 years of age. Safety and efficacy in children younger than 3 years of age have not been established. ^{01}


Geriatrics


No information is available on the relationship of age to the effects of ophthalmic ketotifen in geriatric patients.

Medical considerations/Contraindications
The medical considerations/contraindications included have been selected on the basis of their potential clinical significance (reasons given in parentheses where appropriate)— not necessarily inclusive (» = major clinical significance).


Except under special circumstances, this medication should not be used when the following medical problem exist:
» Hypersensitivity to ketotifen or to any component of the ophthalmic solution, including benzalkonium chloride which is used as the preservative^{01}
Risk-benefit should be considered when the following medical problems exist
» Eye irritation, contact lens-related^{01}    (ketotifen should not be used to treat contact lens related irritation)




Side/Adverse Effects

Note: In clinical trials, the side effects were generally mild and occurrences of the effects was similar to that of the underlying ocular disease being studied^{01}

The following side/adverse effects have been selected on the basis of their potential clinical significance (possible signs and symptoms in parentheses where appropriate)—not necessarily inclusive:

Those indicating need for medical attention
Incidence more frequent
    
Conjunctival injection (eye redness and swelling)—10 to 25%^{01}

Incidence less frequent—Less than 5%
    
Allergic reactions (eye redness; hives; itching; rash), conjunctivitis (eye redness and swelling), eye discharge
eye pain
increased itching of eyes
keratitis (eye redness, swelling and discomfort), rash
^{01}


Those indicating need for medical attention only if they continue or are bothersome
Incidence more frequent—10 to 25%
    
Headaches
rhinitis (stuffy or runny nose )
^{01}
Incidence less frequent—Less than 5%
    
Burning or stinging
dry eyes
eyelid disorder
flu syndrome (fever, tiredness, achiness, and sore throat), lacrimation disorder (tearing), mydriasis (increase in size of pupils ), pharyngitis (sore throat), photophobia ( eye sensitivity to light)

^{01}



Overdose
For more information on the management of overdose or unintentional ingestion, contact a Poison Control Center (see Poison Control Center Listing).

Clinical effects of overdose
No serious signs or symptoms occurred in clinical studies with ingestion of up to 20 mg of ketotifen fumarate. A 5 mL ketotifen bottle is equivalent to 1.725 mg of ketotifen fumarate. ^{01}


Patient Consultation
As an aid to patient consultation, refer to Advice for the Patient, Ketotifen (Ophthalmic).

In providing consultation, consider emphasizing the following selected information (» = major clinical significance):

Before using this medication
  Conditions affecting use, especially:
Hypersensitivity to ketotifen or components of the ophthalmic solution; ketotifen ophthalmic solution contains benzalkonium chloride, a preservative, which may be absorbed by soft contact lenses

Proper use of this medication
» Not wearing contact lenses if the eyes are red; not using ketotifen ophthalmic solution for contact lens–related irritation; removing contact lenses prior to administration; waiting at least 10 minutes after administration before reinserting lenses;

» Proper administration of eye drops

» Proper dosing
Applying as soon as possible; not applying if almost time for next dose; using next dose at regularly scheduled time; not doubling doses.

» Proper storage

Precautions while using this medication
» Checking with physician if symptoms do not improve or if condition worsens


Side/adverse effects
Signs of potential side effects, especially conjunctival injection, allergic reactions, conjunctivitis, eye discharge, eye pain, increased itching of eyes, keratitis, and rash


General Dosing Information
For topical ophthalmic use only. Not for injection or oral use.^{01}

Ketotifen contains benzalkonium chloride, which may be absorbed by soft contact lenses. Contact lenses should be removed prior to administration of ketotifen. Lenses may be reinserted 10 minutes after administration.^{01}


Ophthalmic Dosage Forms

Note: The dosing and strength of the dosage form available are expressed in terms of ketotifen base.


KETOTIFEN FUMARATE OPHTHALMIC SOLUTION

Usual adult and adolescent Dose
Allergic conjunctivitis (prophylaxis)
Topical to the conjunctiva, 1 drop in each affected eye every 8 to 12 hours.^{01}


Usual pediatric dose
Allergic conjunctivitis (prophylaxis)
Children younger than 3 years of age: Safety and efficacy have not been established. ^{01}
Children 3 years of age and older: See Usual adult and adolescent dose.


Strength(s) usually available
U.S.—


0.025% (0.25 mg ketotifen [base] per mL) (Rx) [Zaditor (benzalkonium chloride 0.01%) (glycerol ) (sodium hydroxide/hydrochloric acid) (purified water )]

Note: Each mL contains 0.345 mg ketotifen fumarate, which is equivalent to 0.25 mg ketotifen base. ^{01}


Packaging and storage:
Store between 4 and 25 °C (39 and 77 °F). ^{01}

Auxiliary labeling
   • For the eye.

Developed: 10/13/1999
Revised: 10/28/1999

References

1. Product Information: Zaditor(TM) ketotifen fumarate solution 0.025%. CIBA Vision. Duluth, GA, USA, 8/99.
   

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