NONCLINICAL TOXICOLOGY SECTION.

VisionBlue 0.06% Nonclinical toxicology section. VisionBlue 0.06% Carcinogenesis Mutagenesis Impairment of fertility section. Trypan blue is carcinogenic in rats. Wistar/Lewis rats developed lymphomas after receiving subcutaneous injections of 1% trypan blue dosed at 50 mg/kg every other week for 52 weeks (total does approximately 250,000-fold the maximum recommended human dose of 0.3 mg per injection in 60 kg person, assuming total absorption).Trypan blue was mutagenic in the Ames test and caused DNA strand breaks in vitro.

MECHANISM OF ACTION SECTION.

VisionBlue 0.06% Mechanism of action section. VisionBlue(R) 0.06% selectively stains connective tissue structures in the human eye such as the anterior lens capsule of the human crystalline lens.VisionBlue(R) 0.06% is intended to be applied directly on the anterior lens capsule, staining any portion of the capsule which comes in contact with the dye. Excess dye is washed out of the anterior chamber. The dye does not penetrate the capsule, permitting visualization of the anterior capsule in contrast to the non-stained lens cortex and inner lens material.

HOW SUPPLIED SECTION.

VisionBlue 0.06% How supplied section. VisionBlue(R) 0.06% is supplied as follows:0.5 mL of VisionBlue(R) 0.06% in sterile single-use Luer Lok, 2.25 mL glass syringe, grey rubber plunger stopper and tip cap with polypropylene plunger rod in peel pouch. Ten pouched products are packed in on distribution box.

INDICATIONS & USAGE SECTION.

VisionBlue 0.06% Indications Usage Section. VisionBlue(R) 0.06% is indicated for use as an aid in ophthalmic surgery by staining the anterior capsule of the lens.. HIGHLIGHTS OF PRESCRIBING INFORMATIONThese highlights do not include all the information needed to use VISIONBLUE(R) 0.06% safely and effectively. see full prescribing information for VISIONBLUE(R) 0.06%. VisionBlue(R) (trypan blue ophthalmic solution) 0.06% Initial U.S. Approval: 2004VisionBlue(R) 0.06% is an acid di-azo group dye indicated for use as an aid in ophthalmic surgery by staining the anterior capsule of the lens.

ADVERSE REACTIONS SECTION.

VisionBlue 0.06% Adverse Reactions section. Adverse reactions reported following use of VisionBlue(R) 0.06% include discoloration of high water content hydrogen intraocular lenses (see contraindications) and inadvertent staining of the posterior lens capsule and vitreous face. Staining of the posterior lens capsule or staining of the vitreous face is generally self limited, lasting up to one week.. Inadvertent staining of the posterior lens capsule and vitreous face.To report SUSPECTED ADVERSE REACTIONS contact FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

CARCINOGENESIS & MUTAGENESIS & IMPAIRMENT OF FERTILITY SECTION.

VisionBlue 0.06% Carcinogenesis Mutagenesis Impairment of fertility section. Trypan blue is carcinogenic in rats. Wistar/Lewis rats developed lymphomas after receiving subcutaneous injections of 1% trypan blue dosed at 50 mg/kg every other week for 52 weeks (total does approximately 250,000-fold the maximum recommended human dose of 0.3 mg per injection in 60 kg person, assuming total absorption).Trypan blue was mutagenic in the Ames test and caused DNA strand breaks in vitro.

CLINICAL PHARMACOLOGY SECTION.

VisionBlue 0.06% Clinical Pharmacology section. VisionBlue 0.06% Mechanism of action section. VisionBlue(R) 0.06% selectively stains connective tissue structures in the human eye such as the anterior lens capsule of the human crystalline lens.VisionBlue(R) 0.06% is intended to be applied directly on the anterior lens capsule, staining any portion of the capsule which comes in contact with the dye. Excess dye is washed out of the anterior chamber. The dye does not penetrate the capsule, permitting visualization of the anterior capsule in contrast to the non-stained lens cortex and inner lens material.

CONTRAINDICATIONS SECTION.

VisionBlue 0.06% Contraindications section. VisionBlue(R) 0.06% is contraindicated when non-hydrated (dry state), hydrophilic acrylic intraocular lens (IOL) is planned to be inserted into the eye. The dye may be absorbed by the IOL and stain it.. Insertion of non-hydrated (dry-state), hydrophilic acrylic intraocular lens (IOL).

DESCRIPTION SECTION.

VisionBlue 0.06% Description section. VisionBlue(R) (trypan blue ophthalmic solution) 0.06% is sterile solution of trypan blue (an acid di-azo group dye). VisionBlue(R) 0.06% is selective tissue staining agent for use as medical aid in ophthalmic surgery.Each mL of VisionBlue(R) 0.06% contains: 0.6 mg trypan blue; 1.9 mg sodium mono-hydrogen orthophosphate (Na 2HPO 4.2H 2O); 0.3 mg sodium di-hydrogen orthophosphate (NaH 2PO 4.2H 2O); 8.2 mg sodium chloride (NaCl); and water for injection. The pH is 7.3 7.6. the osmolality is 257-314 mOsm/kg. The drug substance trypan blue has the chemical name 3,3-[(3,3-dimethyl-4,4-biphenylylene) bis (azo)] bis (5-amino-4-hydroxy-2,7-naphthalenedisulfonic acid) tetra sodium salt, molecular weight of 960.8, molecular formula of 34H 24N 6Na 4O 14S 4, and has the following chemical structure: Chemical structure VisionBlue.

DOSAGE & ADMINISTRATION SECTION.

VisionBlue 0.06% Dosage Administration Section. Cataract surgery.VisionBlue(R) 0.06% is packaged in 2.25 mL syringe to which blunt cannula has to be attached.After opening the eye, an air bubble is injected into the anterior chamber of the eye in order to minimize dilution of VisionBlue(R) 0.06% by the aqeous. VisionBlue(R) 0.06% is carefully applied onto the anterior lens capsule using blunt cannula. Sufficient staining is achieved as soon as the dye has contacted the capsule. The anterior chamber is then irrigated with balanced salt solution to remove all excess dye. An anterior capsulotomy can then be performed.. Inject an air bubble into the anterior chamber;Carefully apply VisionBlue(R) 0.06% onto the lens capsule;Remove all excess dye from the anterior chamber.. Inject an air bubble into the anterior chamber;. Carefully apply VisionBlue(R) 0.06% onto the lens capsule;. Remove all excess dye from the anterior chamber.

PREGNANCY SECTION.

VisionBlue 0.06% Pregnancy section. Teratogenic Effects: Pregnancy Category C. Trypan blue is teratogenic in rats, mice, rabbits, hamsters, dogs, guinea pigs, pigs, and chickens. The majority of teratogenicity studies performed involve intravenous, intraperitoneal, or subcutaneous administration in the rat. The teratogenic dose is 50 mg/kg as single dose or 25 mg/kg/day during embryogenesis in the rat. These doses are approximately 10,000- and 5,000-fold the maximum recommended human dose of 0.3 mg per injection based in 60 kg person, assuming that the whole dose is completely absorbed. Characteristic anomalies included neural tube, cardiovascular, vertebral, tail, and eye defects. Trypan blue also caused an increase in post-implantation mortality, and decreased fetal weight. In the monkey, trypan blue caused abortions with single or two daily doses of 50 mg/kg between 20th to 25th days of pregnancy, but no apparent increase in birth defects (approximately 10,000-fold the maximum recommended human daily dose of 0.3 mg per injection, assuming total absorption). There are no adequate and well-controlled studies in pregnant women. Trypan blue should be given to pregnant woman only if the potential benefit justifies the potential risk to the fetus.

SPL UNCLASSIFIED SECTION.

Manufactured byD.O.R.C. International b.v.Scheijdelveweg 23214 VN ZuidlandThe NetherlandsDistributed in the United States byDutch Ophthalmic, USA10 Continental Drive, Bldg 1Exeter, NH 03833, USAPhone: 800-75-DUTCH of 603-778-6929US Patents 6,367,480 and 6,720,314Copyright (C), 2012 Dutch Ophthalmic Research Center.

USE IN SPECIFIC POPULATIONS SECTION.

VisionBlue 0.06% Use in specific populations section. Trypan blue should not be given to pregnant women.. VisionBlue 0.06% Pregnancy section. Teratogenic Effects: Pregnancy Category C. Trypan blue is teratogenic in rats, mice, rabbits, hamsters, dogs, guinea pigs, pigs, and chickens. The majority of teratogenicity studies performed involve intravenous, intraperitoneal, or subcutaneous administration in the rat. The teratogenic dose is 50 mg/kg as single dose or 25 mg/kg/day during embryogenesis in the rat. These doses are approximately 10,000- and 5,000-fold the maximum recommended human dose of 0.3 mg per injection based in 60 kg person, assuming that the whole dose is completely absorbed. Characteristic anomalies included neural tube, cardiovascular, vertebral, tail, and eye defects. Trypan blue also caused an increase in post-implantation mortality, and decreased fetal weight. In the monkey, trypan blue caused abortions with single or two daily doses of 50 mg/kg between 20th to 25th days of pregnancy, but no apparent increase in birth defects (approximately 10,000-fold the maximum recommended human daily dose of 0.3 mg per injection, assuming total absorption). There are no adequate and well-controlled studies in pregnant women. Trypan blue should be given to pregnant woman only if the potential benefit justifies the potential risk to the fetus.. VisionBlue 0.06% Nursing Mothers section. 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 trypan blue is administered to nursing woman.. VisionBlue 0.06% Pediatric use section. The safety and effectiveness of trypan blue have been established in pediatric patients. Use of trypan blue is supported by evidence from an adequate and well-controlled study in pediatric patients.. VisionBlue 0.06% Geriatric use section. No overall differences in safety and effectiveness have been observed between elderly and younger patients.

WARNINGS AND PRECAUTIONS SECTION.

VisionBlue 0.06% Warnings and Precautions section. Excessive staining:It is recommended that after injection all excess VisionBlue(R) 0.06% is immediately removed from the eye by thorough irrigation of the anterior chamber.. Excessive staining: Excess VisionBlue(R) 0.06% should be removed from the eye immediately after staining.