Indications : Conjunctivitis, allergic Pregnancy Category C FDA Approved 1996 Dec DRUG CLASS : Ophthalmics-Decongestants/Antiallergy Ag BRAND NAMES : Patanol (US); DESCRIPTION : Olopatadine HCl ophthalmic solution 0.1% is a sterile ophthalmic solution containing olopatadine, a relatively selective H1-receptor antagonist and inhibitor of histamine release from the mast cell for topical administration to the eyes. Olopatadine HCl is a white, crystalline, water-soluble powder with a molecular weight of 373.88. The chemical name is 11-[(Z)-3-(Dimethylamino)propylidene]-6-11-dihydrodibenz[b,e] oxepin-2-acetic acid hydrochloride. Each ml of olopatadine HCl ophthalmic solution 0.1% contains: Active: 1.11 olopatadine hydrochloride equivalent to 1 mg olopatadine. Preservative: benzalkonium chloride 0.01%. Inactives: dibasic sodium phosphate; sodium chloride; hydrochloric acid/sodium hydroxide (adjust pH); and purified water. CLINICAL PHARMACOLOGY : Olopatadine is an inhibitor of the release of histamine from the mast cell and a relatively selective histamine H1-antagonist that inhibits the in vivo and in vitro type 1 immediate hypersensitivity reaction. Olopatadine is devoid of effects on alpha-adrenergic, dopamine, muscarinic type 1 and 2, and seratonin receptors. Following topical ocular administration in man, olopatadine was shown to have low systemic exposure. Two studies in normal volunteers (totaling 24 subjects) dosed bilaterally with olopatadine 0.15% ophthalmic solution once every 12 hours for 2 weeks demonstrated plasma concentrations to be generally below the quantitation limit of the assay (<0.5 ng/ml). Samples in which olopatadine was quantifiable were typically found within 2 hours of dosing and ranged from 0.5 to 1.3 ng/ml. The half-life in plasma was approximately 3 hours, and ellimination was predominantly through renal excretion. Approximately 60-70% of the dose was recovered in the urine as parent drug. Two metabolites, the mono-desmethyl and the N-oxide, were detected at low concentrations in the urine. Results from conjunctival antigen challenge studies demonstrated that olopatadine HCl ophthalmic solution 0.1%, when subjects were challenged with antigen both initially and up to 8 hours after dosing, was significantly more effective than its vehicle in preventing ocular itching associated with allergic conjunctivitis. INDICATIONS AND USAGE : Olopatadine HCl ophthalmic solution 0.1% is indicated for the temporary prevention of itching of the eye due to allergic conjunctivitis. CONTRAINDICATIONS : Hypersensitivity to any component of this product. WARNINGS : For topical use only. Not for injection. Patients should be instructed not to instill olopatadine HCl ophthalmic solution 0.1% while wearing contact lenses. PRECAUTIONS : Information for Patients : To prevent contaminating the dropper tip and solution, care should be taken not to touch the eyelids or surrounding areas with the dropper tip of the bottle. Keep bottle tightly closed when not in use. Carcinogenesis, Mutagenesis, and Impairment of Fertility : Olopatadine administered orally was not carcinogenic in mice and rats in doses up to 500 mg/kg/day and 200 mg/kg/day, respectively. Based on a 40 mul drop size, these doses were 78,125 and 31,250 times higher than the maximum recommended ocular human dose (MROHD). No mutagenic potential was observed when olopatadine was tested in an in vitro bacterial reverse mutation (Ames) test, an in vitro mammalian chromosome aberration assay or an in vivo mouse micronucleus test. Olopatadine administered to male and female rats at oral doses of 62,500 times MROHD level resulted in a slight decrease in the fertility index and reduced implantation rate; no effects on reproductive function were observed at doses of 7800 times the maximum recommended ocular human use level. Pregnancy Category C : Olopatadine was found not to be teratogenic in rats and rabbits. However, rats treated at 600 mg/kg/day, or 93,750 times the MROHD and rabbits treated at 400 mg/kg/day, or 62,500 times the MROHD, during organogenesis showed a decrease in live fetuses. There are, however no adequated and well controlled studies in pregnant women. Because animal studies are not always predictive of human responses, this drug should be used in pregnant women only if the potential benefit to the mother justifies the potential risk to the embryo or fetus. Nursing Mothers : Olopatadine has been identified in the milk of nursing rats following oral administration. It is not known whether topical ocular administration could result in sufficient systemic absorption to produce detectable quantities in the human breast milk. Nevertheless, caution should be exercised when olopatadine HCl ophthalmic solution 0.1% is administered to a nursing mother. Pediatric Use : Safety and effectiveness in children below the age of 12 have not been established. ADVERSE REACTIONS : Headaches were reported at an incidence of 7%. The following additional ocular and nonocular adverse reactions were reported at an incidence of less than 5%: Ocular : Burning or stinging, dry eye, foreign body sensation, hyperemia, keratitis, lid edema, and pruritis. Nonocular : Asthenia, cold syndrome, pharyngitis, rhinitis, sinusitis, and taste perversion. DOSAGE AND ADMINISTRATION : The recommended dose is one to two drops in each affected eye two times per day at an interval of 6 to 8 hours. PATIENT INFORMATION : Olopatadine is used for prevention of itching of the eye due to allergic conjunctivitis. Inform physician if you are pregnant or nursing. Do not instill while wearing contact lenses. May cause headache, burning or stinging, dry eye, foreign body sensation, redness or inflammation of the eyes, lid swelling and itching, general weakness, cold syndrome, sore throat, rhinitis, sinusitis and tast disturbance. Instill twice daily at 6 to 8 hour intervals. HOW SUPPLIED : Olopatadine HCl ophthalmic solution 0.1% is supplied in 5 ml plastic DROP-TAINER dispensers. Storage : Store at 39° F to 86° F (4° C to 30° C).