LASTACAFT

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 )

Purpose Antihistamine

Directions a dults and children 2 years of age and older: put 1 drop in the affected eye(s) once daily if using other ophthalmic products while using this product, wait at least 5 minutes between each product replace cap after each use c hildren under 2 years of age : consult a doctor

3 DOSAGE FORMS AND STRENGTHS Ophthalmic solution containing alcaftadine 0.25% (2.5 mg/mL). Ophthalmic solution containing alcaftadine 0.25% (2.5 mg/mL) ( 3 )

4 CONTRAINDICATIONS LASTACAFT ® is contraindicated in patients with hypersensitivity to any component in the product. Hypersensitivity ( 4 )

Do not use ■ if solution changes color or becomes cloudy ■ if you are sensitive to any ingredient in this product ■ to treat contact lens related irritation

Stop use and ask a doctor if you experience any of the following: ■ eye pain ■ changes in vision ■ increased redness of the eye ■ itching that worsens or lasts for more than 72 hours

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.

8 USE IN SPECIFIC POPULATIONS 8.1 Pregnancy Risk Summary There are no adequate and well-controlled studies with LASTACAFT® in pregnant women to inform a drug associated risk. There are limited data with the use of alcaftadine eye drops in pregnant women. In embryofetal studies in rats and rabbits, oral administration of alcaftadine during the period of organogenesis did not produce maternal or embryofetal toxicity at clinically relevant doses. Advise pregnant women of a potential risk to the fetus and mother. LASTACAFT® should only be used during pregnancy if the potential benefit justifies the potential risk to the fetus and mother. The background risk of major birth defects and miscarriage for the indicated population is unknown. However, the background risk in the U.S. general population of major birth defects is 2 to 4%, and of miscarriage is 15 to 20%, of clinically recognized pregnancies. Data Animal Data In rats, oral administration of 5, 20 or 40 mg/kg/day alcaftadine during the period of organogenesis (gestational days 6 – 16) caused maternal lethality at doses of 40 mg/kg. The no observed adverse effect level (NOAEL) for maternal toxicity was 20 mg/kg/day (an exposure 230-times higher than that at the maximum recommended human ophthalmic dose [MRHOD], based on AUC). There were no adverse embryofetal effects up to a dose of 20 mg/kg. In rabbits, oral administration of 10, 40 or 80 mg/kg/day alcaftadine during the period of organogenesis (gestational days 6 – 18) caused no maternal toxicity or adverse embryofetal effects up to a dose of 80 mg/kg/day (an exposure 8819-times higher than that at the MRHOD, based on AUC). Daily oral doses of 20 and 30 mg/kg/day alcaftadine administered to rats from Day 6 of pregnancy until Day 20 postpartum produced lower pup weights in offspring. No adverse effects in dams or offspring were observed at doses up to 5 mg/kg/day (a dose 286 times higher than the MRHOD, on a mg/m2 basis). 8. 2 Lac t ation Risk Summary There is no information regarding the presence of LASTACAFT ® in human milk, the effects on the breastfed infants, or the effects on milk production to inform risk of LASTACAFT ® to an infant during lactation. The developmental and health benefits of breastfeeding should be considered, along with the mother’s clinical need for LASTACAFT ® , and any potential adverse effects on the breastfed infant from LASTACAFT ® . 8.4 Pediatric Use Safety and effectiveness in pediatric patients below the age of 2 years have not been established. 8.5 Geriatric Use No overall differences in safety or effectiveness were observed between elderly and younger subjects.

12.1 Mechanism of Action Alcaftadine is an H 1 histamine receptor antagonist and inhibitor of the release of histamine from mast cells. Decreased chemotaxis and inhibition of eosinophil activation has also been demonstrated.

11 DESCRIPTION LASTACAFT® (alcaftadine ophthalmic solution) is an H1 receptor antagonist, in a sterile ophthalmic solution for topical ophthalmic use. Alcaftadine is a white to yellow powder with an empirical formula of C 19 H 21 N 3 O and a molecular weight of 307.39. Contains: Active: alcaftadine 0.25% (2.5 mg/mL) Inactives: benzalkonium chloride 0.005% as a preservative; edetate disodium; sodium phosphate, monobasic; purified water; sodium chloride; sodium hydroxide and/or hydrochloric acid (to adjust pH) Chemical Name: 6,11-dihydro-11-(1-methyl-4-piperidinylidene)-5 H -imidazo[2,1-b] [3] benzazepine-3-carboxaldehyde Structural Formula: The drug product has a pH of approximately 7 and an osmolality of approximately 290 mOsm/kg. The chemical structure for Chemical Name: 6,11-dihydro-11-(1-methyl-4-piperidinylidene)-5H-imidazo[2,1-b] [3] benzazepine-3-carboxaldehyde

Active ingredient Alcaftadine 0.25%

16 HOW SUPPLIED/STORAGE AND HANDLING LASTACAFT ® (alcaftadine ophthalmic solution) 0.25% is supplied in an opaque, white low-density polyethylene bottle with a white polystyrene cap. 3 mL fill in 5 mL bottle NDC 0023-4290-03 Storage: Store at 15°C to 25°C (59°F to 77°F). After opening, LASTACAFT ® can be used until the expiration date on the bottle.