Mireze (Nedocromil Sodium)

MIREZE®

Allergan

Nedocromil Sodium

Antiallergic – Anti-inflammatory

Action And Clinical Pharmacology: Nedocromil displays specific antiallergic and anti-inflammatory properties.

The pharmacological actions of nedocromil in many respects resemble those of sodium cromoglycate, a compound which has been shown to have effects on both the symptoms of ocular allergic inflammation and the level of inflammatory mediators present in the tears. Nedocromil is not only an inhibitor of the immunological release of inflammatory mediators, but also extends this activity to mucosal mast cells, which are thought to play an important role in allergic inflammatory diseases. The conclusion that nedocromil sodium is an anti-inflammatory agent is supported by in vivo observations of its capacity to inhibit the late response to antigen challenge, microvascular leakage and platelet activating factor (PAF) induced bronchoconstriction and hyper-responsiveness. In the dog and guinea-pig, nedocromil sodium has been shown to modify sensory nerve responses, a possible mechanism for its observed inhibitory effects on reflex bronchoconstriction and cough.

When administered as 2% ophthalmic solution in human volunteers, up to 4% of a dose of nedocromil sodium is absorbed; absorption occurs primarily through the nasal mucosa since much of the dose of an ophthalmic solution will drain from the eye via the nasolacrimal duct. Approximately 4 to 8% of an intranasal dose and 2 to 3% of an oral dose of nedocromil sodium is absorbed.

Nedocromil is bound reversibly (up to 89%) to human proteins and to a lesser extent in animals. It is not metabolized in man or animals. In man it is excreted unchanged in the urine (approximately 70%) and in feces (approximately 30%). While the plasma concentration falls rapidly (i.e., 10% of peak levels in 8 hours) and urinary excretion is 90% within 12 hours, fecal eliminations may take up to 3 days to be completed.

Indications And Clinical Uses: For the treatment of seasonal allergic conjunctivitis.

It must be used regularly to ensure optimal control of symptoms.

Treatment should be initiated as closely as possible to the start of the symptoms.

Nedocromil may be used in conjunction with other antiallergic therapies, including topical ophthalmics, (xylometazoline, naphazoline, sodium cromoglycate) topical nasal solutions (xylometazoline, flunisolide, pseudoephedrine) and systemic therapies (e.g., oral antihistamine) as no interactions have been reported.

Contra-Indications: Known hypersensitivity to nedocromil, disodium edetate or benzalkonium chloride.

Manufacturers’ Warnings In Clinical States: Patients who use soft contact lenses must not wear them during the treatment period with Mireze ophthalmic solution. Benzalkonium chloride, a constituent of the formulation, may accumulate in soft contact lenses. This preservative, when slowly released, could possibly irritate the cornea.

In patients who continue to wear hard or gas permeable contact lenses during nedocromil treatment, the lenses should be taken out of the eye prior to instillation of the drops. They should be inserted again not earlier than 5 minutes after administration, in order to allow an even conjunctival distribution of the solution.

To avoid contamination of the contents, patients should not touch the tip of the container or allow the tip of the bottle to come into contact with the eye.

Discard any remaining contents 4 weeks after first opening the bottle.

Precautions: Geriatrics: There is no evidence to suggest that a dose reduction in the elderly is required, as 2% nedocromil sodium ophthalmic solution appears to have a similar activity and safety profile in all groups of patient studied with allergic conjunctivitis. However there is limited clinical trial experience with nedocromil sodium ophthalmic solution, in the elderly.

Children: The safety and efficacy of nedocromil in children under 6 years of age has not yet been established.

Pregnancy: Safety in human pregnancy and the absence of adverse effects on the human reproductive process have not been established. Small amounts of nedocromil are known to cross the placenta but without effect in animals. In fact, in reproductive studies, nedocromil at dosage levels up to 100 mg/kg (more than 800 times the human maintenance dose) has shown no teratogenic or embryotoxic effects, nor has it been observed to interfere with reproductive performance, gestation, parturition, or lactation. Nedocromil has not affected male or female fertility nor has it altered the development of progeny.

Although there is no reason to suspect that nedocromil affects the fetus or mother, as with any drug caution must be exercised, especially during the first trimester. The benefits of treatment to the mother must be weighed against the potential risk to the fetus before proposing its use.

Lactation: Safety in breast-fed infants has not been established. Animal studies have indicated no toxicity of nedocromil in suckling newborns receiving drug from the parent or directly by injection. The concentrations of nedocromil in milk of animals were very low but have not been measured in human milk. The benefits of treating a nursing mother must be weighed against potential risk to the infant.

Drug Interactions: Nedocromil has been given to man in conjunction with other drugs with no apparent ill-effects. These included ophthalmic solutions such as xylometazoline, antazoline and naphazoline, pheniramine, sodium cromoglycate and dexamethasone; topical nasal therapies, such as xylometazoline, flunisolide, pseudoephedrine, chlorpheniramine and beclomethasone diproprionate, and oral antihistamines such as clemastine, astemizole, diphenhydramine, terfenadine, brompheniramine and promethazine.

Nedocromil by inhalation has also been used with inhaled and oral b2-adrenergic agonists, inhaled and oral corticosteroids, theophylline and other methylxanthines and ipratropium bromide. No drug-drug interactions have been observed in humans or in animals.

Adverse Reactions: No major adverse events associated with nedocromil ophthalmic solution have been reported in any of the clinical trials. Only minor adverse effects were reported which were mostly mild and self-limiting.

Symptoms And Treatment Of Overdose: Symptoms and Treatment: There have been no reported cases of overdosage in humans. Animal studies have not shown evidence of toxic effects of nedocromil sodium even at high dosage. If overdosage is suspected, treatment should be supportive and directed to the control of the relevant symptoms.

Dosage And Administration: The ophthalmic solution must be used regularly to ensure optimal control of symptoms.

Treatment should be initiated as closely as possible to the start of the symptoms.

Adults and Children (over 6 years of age): Seasonal Allergic Conjunctivitis: 1 drop into each eye twice daily. Dosage can be increased when necessary to 4 times daily.

Important: Soft contact lenses must not be worn during the treatment period. Benzalkonium chloride, a constituent of the formulation, may accumulate in soft contact lenses. This preservative, when slowly released, could possibly irritate the cornea.

In patients who continue to wear hard or gas permeable contact lenses during treatment, the lenses should be taken out of the eye prior to instillation of the drops. They should be inserted again not earlier than 5 minutes after administration, in order to allow an even conjunctival distribution of the solution.

To avoid contamination of the contents, do not touch any surface with the tip of the container.

Discard any remaining contents 28 days after opening the bottle.

Availability And Storage: Each mL of sterile, aqueous, isotonic, preserved, stabilized, clear pale yellow ophthalmic solution, contains: nedocromil sodium 2% w/v. Nonmedicinal ingredients: benzalkonium chloride, disodium edetate (EDTA), purified water and sodium chloride. White opaque or translucent polyethylene dropper bottles of 2.5, 5 and 10 mL. Drop size is a nominal 0.04 mL, delivering 0.8 mg nedocromil sodium to the eye. Store between 4 and 25°C. Protect from direct sunlight.

MIREZE® Allergan Nedocromil Sodium Antiallergic – Anti-inflammatory

Connected Diseases :

Conjunctivitis

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