ALAMAST^®
(pemirolast potassium ophthalmic solution) 0.1%

ALAMAST^® (pemirolast potassium ophthalmic solution) is a sterile, aqueous ophthalmic solution with a pH of approximately 8.0 containing 0.1% of the mast cell stabilizer, pemirolast potassium, for topical administration to the eyes.

Pemirolast potassium is a slightly yellow, water-soluble powder with a molecular weight of 266.3.

The chemical structure is presented below:

C₁₀H₇KN₆O

Chemical name:
9-methyl-3-(1H-tetrazol-5-yl)-4H-pyrido[1,2-α] pyrimidin-4-one potassium

Each mL contains:ACTIVE: pemirolast potassium 1 mg (0.1%); PRESERVATIVE: lauralkonium chloride 0.005%; INACTIVES: glycerin, dibasic sodium phosphate, monobasic sodium phosphate, phosphoric acid and/or sodium hydroxide to adjust pH, and purified water. The osmolality of ALAMAST^® ophthalmic solution is approximately 240 mOsmol/kg.

Pemirolast potassium is a mast cell stabilizer that inhibits the in vivo Type I immediate hypersensitivity reaction.

In vitro and in vivo studies have demonstrated that pemirolast potassium inhibits the antigen-induced release of inflammatory mediators (e.g., histamine, leukotriene C₄, D₄, E₄) from human mast cells.

In addition, pemirolast potassium inhibits the chemotaxis of eosinophils into ocular tissue and blocks the release of mediators from human eosinophils.

Although the precise mechanism of action is unknown, the drug has been reported to prevent calcium influx into mast cells upon antigen stimulation.

Topical ocular administration of one to two drops of ALAMAST^® ophthalmic solution in each eye four times daily in 16 healthy volunteers for two weeks resulted in detectable concentrations in the plasma. The mean (±SE) peak plasma level of 4.7 ± 0.8 ng/mL occurred at 0.42 ± 0.05 hours and the mean t_1/2 was 4.5 ± 0.2 hours. When a single 10 mg pemirolast potassium dose was taken orally, a peak plasma concentration of 0.723 μg/mL was reached.

Following topical administration, about 10-15% of the dose was excreted unchanged in the urine.

In clinical environmental studies, ALAMAST^® was significantly more effective than placebo after 28 days in preventing ocular itching associated with allergic conjunctivitis.

ALAMAST^® ophthalmic solution is indicated for the prevention of itching of the eye due to allergic conjunctivitis. Symptomatic response to therapy (decreased itching) may be evident within a few days, but frequently requires longer treatment (up to four weeks).

ALAMAST^® ophthalmic solution is contraindicated in patients with previously demonstrated hypersensitivity to any of the ingredients of this product.

For topical ophthalmic use only. Not for injection or oral use.

To prevent contaminating the dropper tip and solution, do not touch the eyelids or surrounding areas with the dropper tip. Keep the bottle tightly closed when not in use.

Patients should be advised not to wear contact lenses if their eye is red. ALAMAST^® should not be used to treat contact lens related irritation. The preservative in ALAMAST^®, lauralkonium chloride, may be absorbed by soft contact lenses. Patients who wear soft contact lenses and whose eyes are not red should be instructed to wait at least ten minutes after instilling ALAMAST^® before they insert their contact lenses.

Pemirolast potassium was not mutagenic or clastogenic when tested in a series of bacterial and mammalian tests for gene mutation and chromosomal injury in vitro nor was it clastogenic when tested in vivo in rats.

Pemirolast potassium had no effect on mating and fertility in rats at oral doses up to 250 mg/kg (approximately 20,000 fold the human dose at 2 drops/eye, 40 μL/drop, QID for a 50 kg adult). A reduced fertility and pregnancy index occurred in the F₁ generation when F₀ dams were treated with 400 mg/kg pemirolast potassium during late pregnancy and lactation period (approximately 30,000 fold the human dose).

Pemirolast potassium is excreted in the milk of lactating rats at concentrations higher than those in plasma. It is not known whether pemirolast potassium is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when ALAMAST^® ophthalmic solution is administered to a nursing woman.

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

In clinical studies lasting up to 17 weeks with ALAMAST^® ophthalmic solution, headache, rhinitis, and cold/flu symptoms were reported at an incidence of 10-25%. The occurrence of these side effects was generally mild. Some of these events were similar to the underlying ocular disease being studied.

The following ocular and non-ocular adverse reactions were reported at an incidence of less than 5%:

Ocular: burning, dry eye, foreign body sensation, and ocular discomfort.

Non-Ocular: allergy, back pain, bronchitis, cough, dysmenorrhea, fever, sinusitis, and sneezing/nasal congestion.

No accounts of ALAMAST^® ophthalmic solution overdose were reported following topical ocular application.

Oral ingestion of the spans of a 10 mL bottle would be equivalent to 10 mg of pemirolast potassium.

Store at 15°-25°C (59°-77°F).

Santen Oy, PO Box 33
FIN-33721 Tampere, Finland

VISTAKON^® Pharmaceuticals, LLC                 U.S. Patent No. 5,034,230
Jacksonville, FL 32256 USA