PACKAGE LABEL.PRINCIPAL DISPLAY PANEL.

NDC 54868-6294-0LASTACAFT(TM)(alcaftadine ophthalmicsolution) 0.25%3 mL Sterile. image of package label.

PEDIATRIC USE SECTION.

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

NONCLINICAL TOXICOLOGY SECTION.

13 NONCLINICAL TOXICOLOGY. 13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility. Alcaftadine was not mutagenic or genotoxic in the Ames test, the mouse lymphoma assay or the mouse micronucleus assay.Alcaftadine was found to have no effect on fertility of male and female rats at oral doses up to 20 mg/kg/day (approximately 200 times the plasma exposure at the recommended human ocular dose).

NURSING MOTHERS SECTION.

8.3 Nursing Mothers. It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when LASTACAFT(TM) is administered to nursing woman.

ADVERSE REACTIONS SECTION.

6 ADVERSE REACTIONS. Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of 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 common ocular adverse reactions, occurring in 4% of LASTACAFT(TM)-treated eyes, were eye irritation, burning and/or stinging on instillation, eye redness, and eye pruritus. (6.1)The most common non-ocular adverse reactions, occurring in 3% of subjects with LASTACAFT(TM)-treated eyes, were nasopharyngitis, headache and influenza. (6.2)To report SUSPECTED ADVERSE REACTIONS, contact Allergan at 1-800-433-8871 or FDA at 1-800-FDA-1088 orwww.fda.gov/medwatch.. 6.1 Ocular Adverse Reactions. The most frequent ocular adverse reactions, occurring in 4% of LASTACAFT(TM)-treated eyes, were eye irritation, burning and/or stinging upon instillation, eye redness and eye pruritus.. 6.2 Non-ocular Adverse Reactions. The most frequent non-ocular adverse reactions, occurring in 3% of subjects with LASTACAFT(TM)-treated eyes, were nasopharyngitis, headache and influenza. Some of these events were similar to the underlying disease being studied.

CARCINOGENESIS & MUTAGENESIS & IMPAIRMENT OF FERTILITY SECTION.

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility. Alcaftadine was not mutagenic or genotoxic in the Ames test, the mouse lymphoma assay or the mouse micronucleus assay.Alcaftadine was found to have no effect on fertility of male and female rats at oral doses up to 20 mg/kg/day (approximately 200 times the plasma exposure at the recommended human ocular dose).

CLINICAL PHARMACOLOGY SECTION.

12 CLINICAL PHARMACOLOGY. 12.1 Mechanism of Action. Alcaftadine is H1 histamine receptor antagonist and inhibitor of the release of histamine from mast cells. Decreased chemotaxis and inhibition of eosinophil activation has also been demonstrated.. 12.3 Pharmacokinetics. AbsorptionFollowing bilateral topical ocular administration of alcaftadine ophthalmic solution, 0.25%, the mean plasma Cmax of alcaftadine was approximately 60 pg/mL and the median Tmax occurred at 15 minutes. Plasma concentrations of alcaftadine were below the lower limit of quantification (10 pg/mL) by hours after dosing. The mean Cmax of the active carboxylic acid metabolite was approximately ng/mL and occurred at 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.. DistributionThe protein binding of alcaftadine and the active metabolite are 39.2% and 62.7%, respectively.. MetabolismThe metabolism of alcaftadine is mediated by non-CYP450 cytosolic enzymes to the active carboxylic acid metabolite.. ExcretionThe elimination half-life of the carboxylic acid metabolite is approximately hours following topical ocular administration. Based on data following oral administration of alcaftadine, the carboxylic acid metabolite is primarily eliminated unchanged in the urine.In vitro studies showed that neither alcaftadine nor the carboxylic acid metabolite substantially inhibited reactions catalyzed by major CYP450 enzymes.

CLINICAL STUDIES SECTION.

14 CLINICAL STUDIES. Clinical efficacy was evaluated in conjunctival allergen challenge (CAC) studies. LASTACAFT(TM) was more effective than its vehicle in preventing ocular itching in patients with allergic conjunctivitis induced by an ocular allergen challenge, both at minutes post-dosing and at 16 hours post-dosing of LASTACAFT(TM).The safety of LASTACAFT(TM) was evaluated in randomized clinical study of 909 subjects over period of weeks.

CONTRAINDICATIONS SECTION.

4 CONTRAINDICATIONS. None.

DESCRIPTION SECTION.

11 DESCRIPTION. LASTACAFT(TM) is sterile, topically administered H1 receptor antagonist containing alcaftadine for ophthalmic use.Alcaftadine is white to yellow powder with an empirical formula of C19H21N3O and molecular weight of 307.39.Contains: Active: alcaftadine 0.25% (2.5 mg/mL). Preservative: benzalkonium chloride 0.005%. Inactives: edetate disodium, monobasic sodium phosphate, purified water, sodium chloride, sodium hydroxide and/or hydrochloric acid to adjust pHChemical Name: 6,11-dihydro-11-(1-methyl-4-piperidinylidene)-5H-imidazo[2,1-b] [3] benzazepine-3-carboxaldehydeStructural Formula:The drug product has pH of approximately and an osmolality of approximately 290 mOsm/kg.. Structural Formula.

DOSAGE & ADMINISTRATION SECTION.

2 DOSAGE AND ADMINISTRATION. Instill one drop in each eye once daily.. Instill one drop in each eye once daily. (2).

DOSAGE FORMS & STRENGTHS SECTION.

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

GERIATRIC USE SECTION.

8.5 Geriatric Use. No overall differences in safety or effectiveness were observed between elderly and younger subjects.

HOW SUPPLIED SECTION.

16 HOW SUPPLIED/STORAGE AND HANDLING. LASTACAFT(TM) (alcaftadine ophthalmic solution) 0.25% is supplied in an opaque, white low-density polyethylene bottle with white polypropylene cap.3 mL fill in mL bottle NDC 54868-6294-0 Storage: Store at 15-25C (59-77F).

INDICATIONS & USAGE SECTION.

1 INDICATIONS AND USAGE. LASTACAFT(TM) is an H1 histamine receptor antagonist indicated for the prevention of itching associated with allergic conjunctivitis.. LASTACAFT(TM) is an H1 histamine receptor antagonist indicated for the prevention of itching associated with allergic conjunctivitis. (1).

INFORMATION FOR PATIENTS SECTION.

17 PATIENT COUNSELING INFORMATION. 17.1 Sterility of Dropper Tip. Patients should be advised to not touch dropper tip to any surface, as this may contaminate the contents.. 17.2 Concomitant Use of Contact Lenses. Patients should be advised not to wear contact lens if their eye is red. Patients should be advised that LASTACAFT(TM) should not be used to treat contact lens-related irritation. Patients should also be advised to remove contact lenses prior to instillation of LASTACAFT(TM). The preservative in LASTACAFT(TM), benzalkonium chloride, may be absorbed by soft contact lenses. Lenses may be reinserted after 10 minutes following administration of LASTACAFT(TM).. 17.3 Topical Ophthalmic Use only. For topical ophthalmic administration only.ALLERGAN Manufactured for Allergan, Inc., Irvine, CA 92612, U.S.A.(C) 2010 Allergan, Inc.(R) and (TM) marks owned by Allergan, Inc.Manufactured in the U.S.A. by JHP Pharmaceuticals, LLC72409US10BRelabeling and Repackaging by: Physicians Total Care, Inc., Tulsa, OK 74146.

MECHANISM OF ACTION SECTION.

12.1 Mechanism of Action. Alcaftadine is H1 histamine receptor antagonist and inhibitor of the release of histamine from mast cells. Decreased chemotaxis and inhibition of eosinophil activation has also been demonstrated.

PHARMACOKINETICS SECTION.

12.3 Pharmacokinetics. AbsorptionFollowing bilateral topical ocular administration of alcaftadine ophthalmic solution, 0.25%, the mean plasma Cmax of alcaftadine was approximately 60 pg/mL and the median Tmax occurred at 15 minutes. Plasma concentrations of alcaftadine were below the lower limit of quantification (10 pg/mL) by hours after dosing. The mean Cmax of the active carboxylic acid metabolite was approximately ng/mL and occurred at 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.. DistributionThe protein binding of alcaftadine and the active metabolite are 39.2% and 62.7%, respectively.. MetabolismThe metabolism of alcaftadine is mediated by non-CYP450 cytosolic enzymes to the active carboxylic acid metabolite.. ExcretionThe elimination half-life of the carboxylic acid metabolite is approximately hours following topical ocular administration. Based on data following oral administration of alcaftadine, the carboxylic acid metabolite is primarily eliminated unchanged in the urine.In vitro studies showed that neither alcaftadine nor the carboxylic acid metabolite substantially inhibited reactions catalyzed by major CYP450 enzymes.

PREGNANCY SECTION.

8.1 Pregnancy. Pregnancy Category B. Reproduction studies performed in rats and rabbits revealed no evidence of impaired female reproduction or harm to the fetus due to alcaftadine. Oral doses in rats and rabbits of 20 and 80 mg/kg/day, respectively, produced plasma exposure levels approximately 200 and 9000 times the plasma exposure at the recommended human ocular dose. There are however, no adequate and well controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed.

SPL UNCLASSIFIED SECTION.

5.1 Contamination of Tip and Solution. To minimize 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.

STORAGE AND HANDLING SECTION.

Storage: Store at 15-25C (59-77F).

USE IN SPECIFIC POPULATIONS SECTION.

8 USE IN SPECIFIC POPULATIONS. 8.1 Pregnancy. Pregnancy Category B. Reproduction studies performed in rats and rabbits revealed no evidence of impaired female reproduction or harm to the fetus due to alcaftadine. Oral doses in rats and rabbits of 20 and 80 mg/kg/day, respectively, produced plasma exposure levels approximately 200 and 9000 times the plasma exposure at the recommended human ocular dose. There are however, no adequate and well controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed.. 8.3 Nursing Mothers. It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when LASTACAFT(TM) is administered to nursing woman.. 8.4 Pediatric Use. Safety and effectiveness in pediatric patients below the age of years have not been established.. 8.5 Geriatric Use. No overall differences in safety or effectiveness were observed between elderly and younger subjects.

WARNINGS AND PRECAUTIONS SECTION.

5 WARNINGS AND PRECAUTIONS. To minimize the risk of contamination, do not touch dropper tip to any surface. Keep bottle tightly closed when not in use. (5.1)LASTACAFT(TM) should not be used to treat contact lens-related irritation. (5.2)Remove contact lenses prior to instillation of LASTACAFT(TM). (5.2). To minimize the risk of contamination, do not touch dropper tip to any surface. Keep bottle tightly closed when not in use. (5.1). LASTACAFT(TM) should not be used to treat contact lens-related irritation. (5.2). Remove contact lenses prior to instillation of LASTACAFT(TM). (5.2). 5.1 Contamination of Tip and Solution. To minimize 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.. 5.2 Contact Lens Use. Patients should be advised not to wear contact lens if their eye is red. LASTACAFT(TM) should not be used to treat contact lens-related irritation.LASTACAFT(TM) should not be instilled while wearing contact lenses. Remove contact lenses prior to instillation of LASTACAFT(TM). The preservative in LASTACAFT(TM), benzalkonium chloride, may be absorbed by soft contact lenses. Lenses may be reinserted after 10 minutes following administration of LASTACAFT(TM).. 5.3 Topical Ophthalmic Use Only. LASTACAFT(TM) is for topical ophthalmic use only.