CLINICAL PHARMACOLOGY SECTION.

12 CLINICAL PHARMACOLOGY 12.2 Pharmacodynamics Maximal corneal anesthesia usually occurs in about 5-45 seconds and lasts about 20 minutes after single administration. The anesthetic effect may be extended by subsequent administration 10-20 minutes after the last administration.

CLINICAL STUDIES SECTION.

14 CLINICAL STUDIES Controlled clinical studies in adults and pediatric patients have demonstrated that topical administration of Fluorescein Sodium and Benoxinate Hydrochloride Ophthalmic Solution, 0.3%/0.4% enables visualization and corneal anesthesia sufficient to enable applanation tonometry, tear fluid dynamics evaluation and short conjunctival and corneal procedures. Maximal corneal anesthesia usually occurs in about 5-45 seconds and lasts about 20 minutes after single administration.

CONTRAINDICATIONS SECTION.

4 CONTRAINDICATIONS Fluorescein Sodium and Benoxinate Hydrochloride Ophthalmic Solution, 0.3%/0.4% is contraindicated in patients with known hypersensitivity to any component of this product.. Known hypersensitivity to any component of this product. (4).

ADVERSE REACTIONS SECTION.

6 ADVERSE REACTIONS The following serious ocular adverse reactions are described elsewhere in the labeling: oCorneal Toxicity [see Warnings and Precautions (5.1)]oCorneal Injury due to Insensitivity [see Warnings and Precautions (5.2)] The following adverse reactions have been identified following use of Fluorescein Sodium and Benoxinate Hydrochloride Ophthalmic Solution, 0.3%/0.4%: ocular hyperemia, burning, stinging, eye irritation, blurred vision and punctate keratitis. Because these reactions are reported voluntarily from population of uncertain size, it is not always possible to reliably estimate their frequency or establish causal relationship to drug exposure. oCorneal Toxicity [see Warnings and Precautions (5.1)]. oCorneal Injury due to Insensitivity [see Warnings and Precautions (5.2)] The most common ocular adverse events are: stinging, burning and conjunctival redness. (6) To report SUSPECTED ADVERSE REACTIONS, contact Bausch Lomb, Division of Valeant Pharmaceuticals North America LLC, or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

CARCINOGENESIS & MUTAGENESIS & IMPAIRMENT OF FERTILITY SECTION.

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility Studies to evaluate the mutagenic or carcinogenic potential of Fluorescein Sodium and Benoxinate Hydrochloride Ophthalmic Solution, 0.3%/0.4% have not been conducted. Studies to evaluate impairment of fertility have not been conducted.

DESCRIPTION SECTION.

11 DESCRIPTION Fluorescein Sodium and Benoxinate Hydrochloride Ophthalmic Solution, 0.3%/0.4% is sterile solution containing disclosing agent in combination with short-acting ester anesthetic for topical ophthalmic use. Fluorescein sodium is represented by the following structural formula: C20H10Na2O5 Mol. Wt. 376.3Chemical Name: 3,6 Dihydroxy-3H-spiro[isobenzofuran-1,9-xanthen]-3-one disodium salt. Benoxinate hydrochloride is represented by the following structural formula: C17H28N2O3 HCl Mol. Wt. 344.88Chemical Name: 2-(Diethylamino) ethyl 4-amino-3-butoxybenzoate hydrochloride.Each mL of Fluorescein Sodium and Benoxinate Hydrochloride Ophthalmic Solution 0.3%/0.4% contains:oActive ingredients: fluorescein sodium 2.6 mg (0.3%) equivalent to fluorescein 2.3 mg (0.2%), benoxinate hydrochloride 4.4 mg (0.4%) equivalent to benoxinate 3.9 mg (0.4%)oPreservative: chlorobutanol 12.6 mg (1.3%)oInactive ingredients: povidone, hydrochloric acid, boric acid, water for injection. Hydrochloric acid may be added to adjust pH (4.3 5.3). C20H10Na2O5 Mol. Wt. 376.3. C17H28N2O3 HCl Mol. Wt. 344.88. oActive ingredients: fluorescein sodium 2.6 mg (0.3%) equivalent to fluorescein 2.3 mg (0.2%), benoxinate hydrochloride 4.4 mg (0.4%) equivalent to benoxinate 3.9 mg (0.4%). oPreservative: chlorobutanol 12.6 mg (1.3%). oInactive ingredients: povidone, hydrochloric acid, boric acid, water for injection. Hydrochloric acid may be added to adjust pH (4.3 5.3). chemstructure1. chemstructure2.

DOSAGE & ADMINISTRATION SECTION.

2 DOSAGE AND ADMINISTRATION Instill to drops topically in the eye as needed. Instill to drops topically in the eye as needed to achieve adequate anesthesia. (2).

DOSAGE FORMS & STRENGTHS SECTION.

3 DOSAGE FORMS AND STRENGTHS Fluorescein Sodium and Benoxinate Hydrochloride Ophthalmic Solution, 0.3%/0.4% is yellow to orange-red ophthalmic solution containing fluorescein sodium 2.6 mg/mL (0.3%) and benoxinate hydrochloride 4.4 mg/mL (0.4%).. Ophthalmic solution containing fluorescein sodium 2.6 mg/mL (0.3%) and benoxinate hydrochloride 4.4 mg/mL (0.4%). (3).

GERIATRIC USE SECTION.

8.5 Geriatric Use No overall differences in safety or effectiveness have been observed between elderly and younger patients.

HOW SUPPLIED SECTION.

16 HOW SUPPLIED/STORAGE AND HANDLING Fluorescein Sodium and Benoxinate Hydrochloride Ophthalmic Solution, 0.3%/0.4% is supplied as sterile, aqueous, topical ophthalmic solution with fill volume of mL in 6 mL amber glass bottle and black polypropylene cap with sterilized rubber dropper bulb and glass pipette. NDC 24208-734-05Storage: Store in refrigerator at 2C to 8C (36F to 46F). Protect from light. After opening, Fluorescein Sodium and Benoxinate Hydrochloride Ophthalmic Solution, 0.3%/0.4% can be stored up to one month if stored at room temperature or until the expiration date on the bottle if stored in refrigerated conditions. Keep tightly closed.

INDICATIONS & USAGE SECTION.

1 INDICATIONS AND USAGE Fluorescein Sodium and Benoxinate Hydrochloride Ophthalmic Solution, 0.3%/0.4% is indicated for ophthalmic procedures in adult and pediatric patients requiring disclosing agent in combination with topical ophthalmic anesthetic agent.. Fluorescein Sodium and Benoxinate Hydrochloride Ophthalmic Solution, 0.3%/0.4% is combination of fluorescein sodium, disclosing agent and benoxinate hydrochloride, local ester anesthetic indicated for procedures in adult and pediatric patients requiring disclosing agent in combination with topical ophthalmic anesthetic. (1).

INFORMATION FOR PATIENTS SECTION.

17 PATIENT COUNSELING INFORMATION Accidental Injury Precaution Advise patients not to touch their eyes for approximately 20 minutes after application. Their eyes will be insensitive due to the effect of the anesthetic, and care should be taken to avoid accidental injuries. Manufactured for and Distributed by:Paragon BioTeck, Inc.4640 SW Macadam Ave, Ste 80Portland, OR 97239Manufactured by: Siegfried-Irvine,9342 Jeronimo Road,Irvine, CA 92618.

LACTATION SECTION.

8.2 Lactation.

NONCLINICAL TOXICOLOGY SECTION.

13 NONCLINICAL TOXICOLOGY 13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility Studies to evaluate the mutagenic or carcinogenic potential of Fluorescein Sodium and Benoxinate Hydrochloride Ophthalmic Solution, 0.3%/0.4% have not been conducted. Studies to evaluate impairment of fertility have not been conducted.

PACKAGE LABEL.PRINCIPAL DISPLAY PANEL.

PACKAGE/LABEL PRINCIPAL DISPLAY PANEL NDC 24208-734-05ParagonBioTeck, Inc.FluoresceinSodium and BenoxinateHydrochlorideOphthalmicSolution,0.3%/0/4%Rx Only5 mL. carton.

PEDIATRIC USE SECTION.

8.4 Pediatric Use The safety and effectiveness of Fluorescein Sodium and Benoxinate Hydrochloride Ophthalmic Solution, 0.3%/0.4% have been established for pediatric patients. Use of Fluorescein Sodium and Benoxinate Hydrochloride Ophthalmic Solution, 0.3%/0.4% is supported in pediatric patients by evidence from adequate and well controlled studies.

PHARMACODYNAMICS SECTION.

12.2 Pharmacodynamics Maximal corneal anesthesia usually occurs in about 5-45 seconds and lasts about 20 minutes after single administration. The anesthetic effect may be extended by subsequent administration 10-20 minutes after the last administration.

PREGNANCY SECTION.

8.1 Pregnancy.

SPL UNCLASSIFIED SECTION.

5.1 Corneal Toxicity Prolonged use or abuse may lead to corneal epithelial toxicity and may manifest as epithelial defects which may progress to permanent corneal damage with accompanying visual loss.

USE IN SPECIFIC POPULATIONS SECTION.

8 USE IN SPECIFIC POPULATIONS 8.1 Pregnancy 8.2 Lactation 8.4 Pediatric Use The safety and effectiveness of Fluorescein Sodium and Benoxinate Hydrochloride Ophthalmic Solution, 0.3%/0.4% have been established for pediatric patients. Use of Fluorescein Sodium and Benoxinate Hydrochloride Ophthalmic Solution, 0.3%/0.4% is supported in pediatric patients by evidence from adequate and well controlled studies.. 8.5 Geriatric Use No overall differences in safety or effectiveness have been observed between elderly and younger patients.

WARNINGS AND PRECAUTIONS SECTION.

5 WARNINGS AND PRECAUTIONS oCorneal Toxicity: Prolonged use or abuse may lead to corneal epithelial toxicity and manifest as epithelial defects which may progress to permanent corneal damage. (5.1)oCorneal Injury: Patients should not touch the eye for approximately 20 minutes after using anesthetic as accidental injuries can occur due to insensitivity of the eye. (5.2). oCorneal Toxicity: Prolonged use or abuse may lead to corneal epithelial toxicity and manifest as epithelial defects which may progress to permanent corneal damage. (5.1). oCorneal Injury: Patients should not touch the eye for approximately 20 minutes after using anesthetic as accidental injuries can occur due to insensitivity of the eye. (5.2). 5.1 Corneal Toxicity Prolonged use or abuse may lead to corneal epithelial toxicity and may manifest as epithelial defects which may progress to permanent corneal damage with accompanying visual loss.. 5.2 Corneal Injury due to Insensitivity Patients should not touch the eye for approximately 20 minutes after using this anesthetic as accidental injuries can occur due to insensitivity of the eye.