Alcaftadine

1 INDICATIONS AND USAGE LASTACAFT ® is an H 1 histamine receptor antagonist indicated for the prevention of itching associated with allergic conjunctivitis. LASTACAFT ® is an H 1 histamine receptor antagonist indicated for the prevention of itching associated with allergic conjunctivitis. ( 1 )

2 DOSAGE AND ADMINISTRATION Instill one drop in each eye once daily. If more than 1 topical ophthalmic medicinal product is being used, each one should be administered at least 5 minutes apart. Instill one drop in each eye once daily. ( 2 )

6 ADVERSE REACTIONS The most common ocular adverse reactions, occurring in less than 4% of eyes treated with LASTACAFT ® , were eye irritation, burning and/or stinging on instillation, eye redness, and eye pruritus. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Allergan at 1-800-678-1605 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice. The most frequent ocular adverse reactions, occurring in less than 4% of eyes treated with LASTACAFT ® , were eye irritation, burning and/or stinging upon instillation, eye redness and eye pruritus. The most frequent non-ocular adverse reactions, occurring in less than 3% of subjects with eyes treated with LASTACAFT ® , were nasopharyngitis and headache. Some of these events were similar to the underlying disease being studied. 6. 2 Postmarketing Experience The following adverse reactions have been identified during post-approval use of LASTACAFT ® . Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. These reactions include eye discharge, eye swelling, erythema of eyelid, eyelid edema, lacrimation increased, vision blurred, hypersensitivity reactions including swelling of the face or allergic dermatitis, and somnolence.

12.3 Pharmacokinetics Absorption Following bilateral topical ocular administration of alcaftadine ophthalmic solution, 0.25%, the mean plasma C max of alcaftadine was approximately 60 pg/mL and the median T max occurred at 15 minutes. Plasma concentrations of alcaftadine were below the lower limit of quantification (10 pg/mL) by 3 hours after dosing. The mean C max of the active carboxylic acid metabolite was approximately 3 ng/mL and occurred at 1 hour after dosing. Plasma concentrations of the carboxylic acid metabolite were below the lower limit of quantification (100 pg/mL) by 12 hours after dosing. There was no indication of systemic accumulation or changes in plasma exposure of alcaftadine or the active metabolite following daily topical ocular administration. Distribution The protein binding of alcaftadine and the active metabolite are 39.2% and 62.7%, respectively. Elimination Metabolism The metabolism of alcaftadine is mediated by non-CYP450 cytosolic enzymes to the active carboxylic acid metabolite. In vitro studies showed that neither alcaftadine nor the carboxylic acid metabolite substantially inhibited reactions catalyzed by major CYP450 enzymes. Excretion The elimination half-life of the carboxylic acid metabolite is approximately 2 hours following topical ocular administration. Based on data following oral administration of alcaftadine, the carboxylic acid metabolite is primarily eliminated unchanged in the urine.