ALOCRIL™ (nedocromil sodium ophthalmic solution) 2% is a clear, yellow, sterile solution for topical ophthalmic use.

Nedocromil sodium is represented by the following structural formula:

Chemical Name: 4H-Pyrano[3,2-g] quinoline-2, 8-dicarboxylic acid, 9-ethyl-6, 9-dihydro-4, 6-dioxo-10-propyl-, disodium salt.

Each mL contains: Active: Nedocromil sodium 20 mg (2%); Preservative Benzalkonium chloride 0.01%; Inactives: Sodium chloride 0.5%, edetate disodium 0.05% and purified water. It has a pH of 4.0 to 5.5.

Nedocromil sodium is a mast cell stabilizer. Nedocromil sodium inhibits the release of mediators from cells involved in hypersensitivity reactions. Decreased chemotaxis and decreased activation of eosinophils have also been demonstrated.

In vitro studies with adult human bronchoalveolar cells showed that nedocromil sodium inhibits histamine release from a population of mast cells having been defined as belonging to the mucosal sub type and beta-glucuronidase release from macrophages.

and Bioavailability

Nedocromil sodium exhibits low systemic absorption. When administered as a 2% ophthalmic solution in adult human volunteers, less than 4% of the total dose was systemically absorbed following multiple dosing. Absorption is mainly through the nasolacrimal duct rather than through the conjunctiva. It is not metabolized and is eliminated primarily unchanged in urine (70%) and feces (30%).

ALOCRIL™ is indicated for the treatment of itching associated with allergic conjunctivitis.

CONTRAINDICATIONS

ALOCRIL™ is contraindicated in those patients who have shown hypersensitivity to nedocromil sodium or to any of the other ingredients.

PRECAUTIONS

Information for Patients

Patients should be advised to follow the patient instructions listed on the Information for Patients sheet.

Users of contact lenses should refrain from wearing lenses while exhibiting the signs and symptoms of allergic conjunctivitis.

Carcinogenesis, Mutagenesis, and Impairment of Fertility

A two-year inhalation carcinogenicity study of nedocromil sodium at a dose of 24 mg/kg/day (approximately 400 times the maximum recommended human daily ocular dose on a mg/kg basis) in Wistar rats showed no carcinogenic potential.

Nedocromil sodium showed no mutagenic potential in the Ames Salmonella/microsome plate assay, mitotic gene conversion in Saccharomyces cerevisiae, mouse lymphoma forward mutation and mouse micronucleus assays.

Reproduction and fertility studies in mice and rats showed no effects on male and female fertility at a subcutaneous dose of 100 mg/kg/day (more than 1600 times the maximum recommended human daily ocular dose).

Pregnancy: Teratogenic Effects: Pregnancy Category B

Reproduction studies performed in mice, rats and rabbits using a subcutaneous dose of 100 mg/kg/day (more than 1600 times the maximum human daily ocular dose on a mg/kg basis) revealed no evidence of teratogenicity or harm to the fetus due to nedocromil sodium. There are, however, no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, ALOCRIL™ should be used during pregnancy only if clearly needed.

Nursing Mothers

After intravenous administration to lactating rats, nedocromil was excreted in milk. It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when ALOCRIL™ is administered to a nursing woman.

Pediatric Use

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

Geriatric Use

No overall differences in safety or effectiveness have been observed between elderly and younger patients.

ADVERSE REACTIONS

The most frequently reported adverse experience was headache (~40%).

Ocular burning, irritation and stinging, unpleasant taste, and nasal congestion have been reported to occur in 10-30% of patients. Other events occurring between 1-10% included asthma, conjunctivitis, eye redness, photophobia, and rhinitis.

Some of these events were similar to the underlying ocular disease being studied.

DOSAGE AND ADMINISTRATION

The recommended dosage is one or two drops in each eye twice a day. ALOCRIL™ should be used at regular intervals.

Treatment should be continued throughout the period of exposure (i.e., until the pollen season is over or until exposure to the offending allergen is terminated), even when symptoms are absent.

HOW SUPPLIED

ALOCRIL™ (nedocromil sodium ophthalmic solution) 2% is supplied as 5 mL of solution in a natural, low-density polyethylene round eye drop bottle with a controlled dropper tip, and a natural polypropylene cap.

5 mL NDC 0023-8842-05

Storage

Store between 2°-25°C (36°-77°F). Keep tightly closed and out of the reach of children.

Rx Only

Manufactured by

Laboratoires FISONS SA

Le Trait, France

Distributed by

Allergan

Irvine, CA 92612, USA

8729X

PRODUCT PHOTO(S):

NOTE: These photos can be used only for identification by shape, color, and imprint. They do not depict actual or relative size.

The product samples shown here have been supplied by the manufacturer and reproduced in full color by PDR as a quick-reference identification aid. While every effort has been made to assure accurate reproduction, please remember that any visual identification should be considered preliminary. In cases of poisoning or suspected overdosage, the drug' identity should be verified by chemical analysis.