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Emedastine (Ophthalmic)


VA CLASSIFICATION
Primary: OP801

Commonly used brand name(s): Emadine.

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



Category:


Antihistamine (H 1-receptor), ophthalmic—

antiallergic, ophthalmic—

Indications

Accepted

Conjunctivitis, allergic (treatment)—Ophthalmic emedastine is indicated for temporary relief of the symptoms of allergic conjunctivitis {01}.


Pharmacology/Pharmacokinetics

Physicochemical characteristics:
Molecular weight—
    Emedastine difumarate: 534.57 {01}


pH
    Approximately 7.4 {01}.

Mechanism of action/Effect:

Emedastine is a relatively selective histamine H 1-receptor antagonist according to in vitro studies. Topical ocular administration of emedastine produces concentration-dependent inhibition of histamine-stimulated vascular permeability in the conjunctiva. Emedastine does not affect adrenergic, dopamine, or serotonin receptors. {01}

Absorption:

Ophthalmic use of emedastine usually does not produce measurable plasma concentrations. A study in normal volunteers (10 subjects) who were administered emedastine 0.05% ophthalmic solution in each eye twice a day for 16 days found that plasma concentrations were generally below the quantitative limit of the assay (less than 0.3 nanogram per mL). Samples in which emedastine was quantifiable contained plasma concentrations ranging from 0.3 to 0.49 nanogram per mL. {01}

Biotransformation:

Two primary metabolites, 5- and 6-hydroxyemedastine, are found in the urine as both free and conjugated forms. Minor metabolites include the 5´-oxoanalogs of 5- and 6-hydroxyemedastine and the N-oxide. {01}

Half-life:

Elimination—3 or 4 hours {01}.

Elimination:
    Renal, approximately 44% of an oral dose over 24 hours (3.6% unchanged) {01}.


Precautions to Consider

Carcinogenicity

No evidence of carcinogenicity was found in lifetime studies in mice and rats given dietary doses of emedastine that were more than 80,000 times and 26,000 times, respectively, the maximum recommended ocular human use level of 0.002 mg per kg of body weight (mg/kg) per day for a 50-kg adult {01}.

Mutagenicity

Emedastine was not found to be mutagenic in in vitro tests, including a bacterial reverse mutation (Ames) test, a modification of the Ames test, a mammalian chromosome aberration test, a mammalian forward mutation test, and a mammalian DNA repair synthesis test, or in in vivo tests including a mammalian sister chromatid exchange test and a mouse micronucleus test. {01}

Pregnancy/Reproduction
Fertility—
Studies in rats given doses of emedastine that were 15,000 times the maximum recommended ocular human use level found no evidence of impairment of fertility or reproductive capacity {01}.

Pregnancy—
Adequate and well-controlled studies in humans have not been done {01}.

Studies in rats and rabbits given doses of emedastine that were 15,000 times the maximum recommended ocular human use level found no evidence of teratogenicity, and the same dose produced no effect on perinatal or postnatal development in rats. However, studies in rats given doses of emedastine that were 70,000 times the maximum recommended ocular human use level found an increased incidence of external, visceral, and skeletal anomalies. {01}

FDA Pregnancy Category B {01}.

Breast-feeding

It is not known whether ophthalmic emedastine is absorbed in sufficient quantities to be distributed into human breast milk. However, emedastine has been detected in the milk of lactating rats following oral administration. Risk-benefit should be considered before use of ophthalmic emedastine during breast-feeding. {01}

Pediatrics

Appropriate studies on the relationship of age to the effects of ophthalmic emedastine have not been performed in children up to 3 years of age. Safety and efficacy have not been established. {01}


Geriatrics


No information is available on the relationship of age to the effects of ophthalmic emedastine 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).


Risk-benefit should be considered when the following medical problem exists
» Sensitivity to emedastine{01}


Side/Adverse Effects
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 less frequent—Less than 5%
    
Abnormal dreams{01}
    
asthenia{01} (weakness)
    
corneal infiltrates{01} or staining{01} (blurred vision or other change in vision)
    
keratitis{01} (eye redness, irritation, or pain)
    
tearing{01} , discomfort{01} , or other eye irritation not present before therapy or becoming worse during therapy



Those indicating need for medical attention only if they continue or are bothersome
Incidence more frequent
    
Headache{01} —11%

Incidence less frequent—Less than 5%
    
Bad taste{01}
    
burning or stinging of the eye{01}
    
dermatitis{01} (skin rash or itching)
    
dry eye{01}
    
foreign body sensation{01} (feeling of something in the eye)
    
hyperemia{01} (redness of eye)
    
pruritis{01} (itching)
    
rhinitis{01} (stuffy or runny nose)
    
sinusitis{01} (headache or runny nose)





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



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

Before using this medication
»   Conditions affecting use, especially:
Sensitivity to emedastine





Breast-feeding—Detected in the milk of lactating rats following oral administration of emedastine

Proper use of this medication
» Not wearing contact lenses if eyes are red; if eyes are not red, removing contact lenses prior to administration; waiting at least 10 minutes after administration before reinserting lenses {01}

» Proper administration; not touching applicator tip to any surface; keeping container tightly closed

» Proper dosing
Missed dose: Using as soon as possible; not using if almost time for next dose; using next dose at regularly scheduled time

» 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 abnormal dreams; asthenia; corneal infiltrates or staining; keratitis; sinusitis; and tearing, discomfort, or other eye irritation not present before therapy or becoming worse during therapy


General Dosing Information
Emedastine contains benzalkonium chloride, which may be absorbed by contact lenses. The manufacturer does not recommend use of contact lenses if eyes are red. If eyes are not red, contact lenses should be removed prior to administration of emedastine and may be reinserted 10 minutes after administration {01}.


Ophthalmic Dosage Forms

EMEDASTINE DIFUMARATE OPHTHALMIC SOLUTION

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


Usual adult and adolescent dose
Allergic conjunctivitis
Topical, to the conjunctiva, 1 drop in each affected eye up to four times a day {01}.


Usual pediatric dose
Allergic conjunctivitis
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.—


0.05% (Rx) [Emadine (benzalkonium chloride 0.01%) (tromethamine) ( sodium chloride) (hydroxypropyl methylcellulose ) (hydrochloric acid/sodium hydroxide) (purified water)]

Note: Each mL contains 0.884 mg emedastine difumarate, which is equivalent to 0.5 mg emedastine base {01}.


Packaging and storage:
Store between 4 and 30 °C (39 and 86 °F) {01}.

Auxiliary labeling:
   • For the eye.



Developed: 08/14/1998



References
  1. Emadine package insert (Alcon—US), Rev 12/97, Rec 3/20/98.
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