NEDOCROMIL: 34 Adverse Event Reports & Safety Profile

DESCRIPTION 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 N ame: 4 H -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/mL (2%); Preservative: Benzalkonium chloride 0.01%; Inactives : Edetate disodium 0.05%, purified water, and sodium chloride 0.5%. It has a pH range of 4.0 to 5.5 and an osmolality range of 270 to 330 mOsm/kg. Nedocromil sodium is represented by the following structural formula:

INDICATIONS AND USAGE ALOCRIL ® ophthalmic solution is indicated for the treatment of itching associated with allergic conjunctivitis.

DOSAGE AND ADMINISTRATION The recommended dosage is one or two drops in each eye twice a day. ALOCRIL ® ophthalmic solution 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.

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

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.

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. Patients should be instructed to avoid allowing the tip of the dispensing container to contact the eye, surrounding structures, fingers, or any other surface in order to avoid contamination of the solution by common bacteria known to cause ocular infections. Serious damage to the eye and subsequent loss of vision may result from using contaminated solutions. 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

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 ® ophthalmic solution 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 ® ophthalmic solution 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.