olopatadine hydrochloride 0.665 MG/ACTUAT Metered Dose Nasal Spray [PATANASE]

INDICATIONS AND USAGE Olopatadine hydrochloride nasal solution (nasal spray) is indicated for the relief of the symptoms of seasonal allergic rhinitis in adults and pediatric patients 6 years of age and older. Olopatadine hydrochloride nasal solution (nasal spray) is an H 1 receptor antagonist indicated for the relief of the symptoms of seasonal allergic rhinitis in adults and pediatric patients 6 years of age and older.

DOSAGE AND ADMINISTRATION For nasal use only. Recommended dosages: • Adults and Adolescents ≥ 12 Years : Two sprays per nostril (665 mcg per spray) twice daily ( 2.1 ). • Pediatric Patients 6 to 11 Years : One spray per nostril (665 mcg per spray) twice daily ( 2.2 ). • Priming Information : Prime olopatadine hydrochloride nasal solution (nasal spray) before initial use and when olopatadine hydrochloride nasal solution (nasal spray) has not been used for more than 7 days ( 2.3 ). 2.1 Adults and Adolescents Twelve Years of Age and Older The recommended dosage is two sprays per nostril twice daily. 2.2 Pediatric Patients Six to Eleven Years of Age The recommended dosage is one spray per nostril twice daily. 2.3 Administration Information Administer olopatadine hydrochloride nasal solution (nasal spray) by the nasal route only. Priming : Before initial use, prime olopatadine hydrochloride nasal solution (nasal spray) by releasing 5 sprays or until a fine mist appears. The correct amount of medication cannot be assured before the initial priming. Re-priming (as needed): When olopatadine hydrochloride nasal solution (nasal spray) has not been used for more than 7 days, re-prime by releasing 2 sprays. Avoid spraying olopatadine hydrochloride nasal solution (nasal spray) into the eyes. Discard Instructions : Discard nasal device after 240 sprays (enough for 30 days of dosing) have been used even though the bottle is not completely empty. The correct amount of medication cannot be assured after 240 sprays have been used.

WARNINGS AND PRECAUTIONS • Epistaxis, Nasal Ulceration, and Nasal Septal Perforation : Monitor patients periodically for signs of adverse effects on the nasal mucosa. Discontinue if ulcerations or perforations occur. Avoid use in patients with nasal disease other than allergic rhinitis ( 5.1 ). • Avoid engaging in hazardous occupations requiring complete mental alertness and coordination, such as driving or operating machinery when taking olopatadine hydrochloride nasal solution (nasal spray) ( 5.2 ). • Avoid concurrent use of alcohol or other central nervous system depressants with olopatadine hydrochloride nasal solution (nasal spray) ( 5.2 ). 5.1 Local Nasal Effects Epistaxis and Nasal Ulceration In placebo-controlled clinical trials (vehicle nasal spray) of 2 weeks to 12 months duration, epistaxis and nasal ulcerations were reported [ see Adverse Reactions 6.1 ]. Nasal Septal Perforation Three placebo-controlled long term (12 months) safety trials (vehicle nasal spray) were conducted. In the first safety trial, patients were treated with an investigational formulation of olopatadine hydrochloride nasal solution (nasal spray) containing povidone (not the commercially marketed formulation) or a vehicle nasal spray containing povidone. Nasal septal perforations were reported in one patient treated with the investigational formulation of olopatadine hydrochloride nasal solution (nasal spray) and 2 patients treated with the vehicle nasal spray. In the second safety trial with olopatadine hydrochloride nasal solution (nasal spray), which does not contain povidone, there were no reports of nasal septal perforation. In the third safety trial, one patient exposed to the 3.7 pH vehicle nasal spray (containing no povidone) reported a nasal septal perforation [ see Adverse Reactions ( 6.1 ) ]. Before starting olopatadine hydrochloride nasal solution (nasal spray), conduct a nasal examination to ensure that patients are free of nasal disease other than allergic rhinitis. Perform nasal examinations periodically for signs of adverse effects on the nasal mucosa and consider stopping olopatadine hydrochloride nasal solution (nasal spray) if patients develop nasal ulcerations. 5.2 Somnolence and Impaired Mental Alertness In clinical trials, the occurrence of somnolence has been reported in some patients taking olopatadine hydrochloride nasal solution (nasal spray) [ see Adverse Reactions ( 6.1 ) ]. Patients should be cautioned against engaging in hazardous occupations requiring complete mental alertness and motor coordination such as driving or operating machinery after administration of olopatadine hydrochloride nasal solution (nasal spray). Concurrent use of olopatadine hydrochloride nasal solution (nasal spray) with alcohol or other central nervous system depressants should be avoided because additional reductions in alertness and additional impairment of central nervous system performance may occur.

CONTRAINDICATIONS Olopatadine hydrochloride ophthalmic solution USP, 0.1% is contraindicated in persons with a known hypersensitivity to olopatadine hydrochloride, USP or any components of olopatadine hydrochloride ophthalmic solution USP, 0.1%.

CLINICAL PHARMACOLOGY Olopatadine is an inhibitor of the release of histamine from the mast cell and a relatively selective histamine H 1 -antagonist that inhibits the in vivo and in vitro type 1 immediate hypersensitivity reaction including inhibition of histamine induced effects on human conjunctival epithelial cells. Olopatadine is devoid of effects on alpha-adrenergic, dopamine and muscarinic type 1 and 2 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 elimination 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 an environmental study demonstrated that olopatadine hydrochloride ophthalmic solution USP, 0.1% was effective in the treatment of the signs and symptoms of allergic conjunctivitis when dosed twice daily for up to 6 weeks. Results from conjunctival antigen challenge studies demonstrated that Olopatadine hydrochloride ophthalmic solution USP, 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.