ADVERSE REACTIONS SECTION.

MembraneBlue 0.15% Adverse reactions section.. Adverse reactions reported following use of MembraneBlue(TM) 0.15% 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.. Discoloration of high water content hydrogen intraocular lenses;Inadvertent staining of the posterior lens capsule and vitreous face;To report suspected adverse reactions contact Dutch Ophthalmic, USA at 1-800-75-DUTCH or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch Discoloration of high water content hydrogen intraocular lenses;. Inadvertent staining of the posterior lens capsule and vitreous face;.

CLINICAL PHARMACOLOGY SECTION.

MembraneBlue 0.15% Clinical Pharmacology Section.. MembraneBlue 0.15% Mechanism of action section.. MembraneBlue(TM) 0.15% selectively stains membranes in the human eye during posterior surgery, such as epiretinal membranes (ERM) and Internal Limiting Membranes (ILM).

CONTRAINDICATIONS SECTION.

MembraneBlue 0.15% Contraindications section.. MembraneBlue(TM) 0.15% 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.

MembraneBlue 0.15% Description.. MembraneBlue(TM) 0.15% (trypan blue ophthalmic solution) is sterile solution of trypan blue (an acid di-azo group dye). MembraneBlue(TM) 0.15% selectively stains epiretinal membranes during ophthalmic surgical vitrectomy procedures.Each mL of MembraneBlue(TM) 0.15% contains: 1.5 mg trypan blue; 1.9 mg sodium mono-hydrogen orthophosphate (Na 2HPO 4o2H 2O); 0.3 mg sodium di-hydrogen orthophosphate (NaH 2PO 4o2H 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 MembraneBlue.

DOSAGE & ADMINISTRATION SECTION.

MembraneBlue 0.15% Dosage administration section. Make sure the plunger moves smoothly before use. Prime the syringe prior to use by retracting the plunger before injecting the fluid. Alternatively, twist the plunger into the stopper in clockwise motion until tight. Once tight, continue turning the plunger in clockwise motion until the stopper rotates freely within the syringe, two or three rotations. The syringe is now primed and suitable for injection.Before injection of MembraneBlue(TM) 0.15% perform fluid-air exchange, i.e. filling the entire vitreous cavity with air, to prevent aqeous dilution of MembraneBlue(TM) 0.15%. MembraneBlue(TM) 0.15% is carefully applied to the retinal membrane using blunt cannula attached to the MembraneBlue(TM) 0.15% syringe, without allowing the cannula to contact or damage the retina. Sufficient staining is expected on contact with the membrane. All excess dye should be removed from the vitreous cavity before performing an air-fluid exchange, to prevent unnecessary spreading of the dye.MembraneBlue(TM) 0.15% can also be injected directly in BSS filled vitreous cavity (instead of injecting under air). Clinical use demonstrated that, after complete vitreous and posterior hyaloid removal, sufficient staining is achieved after 30 seconds of application under BSS.MembraneBlue(TM) 0.15% is intended to be applied directly on the areas where membranes could be present, staining any portion of the membrane which comes in contact with the dye. The dye does not penetrate the membrane.. Prior to injection of MembraneBlue(TM) 0.15% perform fluid-air exchange; Carefully apply MembraneBlue(TM) 0.15% to epiretinal membranes using blunt cannula; Remove all excess dye; OrInject MembraneBlue(TM) 0.15% directly in BSS filled vitreous cavity; Wait 30 seconds; Remove all excess dye.. Prior to injection of MembraneBlue(TM) 0.15% perform fluid-air exchange; Carefully apply MembraneBlue(TM) 0.15% to epiretinal membranes using blunt cannula; Remove all excess dye; Or. Inject MembraneBlue(TM) 0.15% directly in BSS filled vitreous cavity; Wait 30 seconds; Remove all excess dye.

DOSAGE FORMS & STRENGTHS SECTION.

MembraneBlue 0.15% Dosage forms strengths section.. MembraneBlue(TM) 0.15% (trypan blue ophthalmic solution) is supplied in 2.25 mL syringes filled to volume of 0.5 mL.. MembraneBlue(TM) 0.15% (trypan blue ophthalmic solution) in volume of 0.5 mL.

GERIATRIC USE SECTION.

MembraneBlue 0.15% Geriatric use.. No overall differences in safety and effectiveness have been observed between elderly and younger patients.

HOW SUPPLIED SECTION.

MembraneBlue 0.15% How supplied section.. MembraneBlue(TM) 0.15% is supplied as follows:0.5 mL of MembraneBlue(TM) 0.15% 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. Five pouched products are packed in one distribution box.

INDICATIONS & USAGE SECTION.

MembraneBlue 0.15% Indications Usage Section. MembraneBlue(TM) 0.15% is indicated for use as an aid in ophthalmic surgery by staining the epiretinal membranes during ophthalmic surgical vitrectomy procedures, facilitating removal of the tissue.. HIGHLIGHTS OF PRESCRIBING INFORMATIONThese highlights do not include all the information needed to use MembraneBlue(TM) 0.15% safely and effectively. See full prescribing information for MembraneBlue(TM) 0.15%. MembraneBlue(TM) 0.15% (trypan blue ophthalmic solution) Initial U.S. Approval: 2004For use as an aid in ophthalmic posterior surgery;Facilitating removal of epiretinal tissue.. For use as an aid in ophthalmic posterior surgery;. Facilitating removal of epiretinal tissue.

MECHANISM OF ACTION SECTION.

MembraneBlue 0.15% Mechanism of action section.. MembraneBlue(TM) 0.15% selectively stains membranes in the human eye during posterior surgery, such as epiretinal membranes (ERM) and Internal Limiting Membranes (ILM).

NONCLINICAL TOXICOLOGY SECTION.

MembraneBlue 0.15% Nonclinical toxicology section.. Trypan blue is carcinogenic in rats. Wister/Lewis rats developed lymphomas after receiving subcutaneous injections of 1% trypan blue dosed at 50 mg/kg every other week for 52 weeks (total dose approximately 100,000-fold the maximum recommended human dose of 0.75 mg per injection in 60 kg person,assuming total absorption).

NURSING MOTHERS SECTION.

MembraneBlue 0.15% 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.

PACKAGE LABEL.PRINCIPAL DISPLAY PANEL.

MembraneBlue 0.15% Package label.Principal display panel. MembraneBlue Box. MembraneBlue labelling.

PEDIATRIC USE SECTION.

MembraneBlue 0.15% 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.

PREGNANCY SECTION.

MembraneBlue 0.15% 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 4,000- and 2,000-fold the maximum recommended human dose of 0.75 mg per injection based on 60 kg person, assuming that the whole dose is completely absorved. 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 the 20th to 25th days of pregnancy, but no apparent increase in birth defects (approximately 4,000-fold maximum recommended human dose of 0.75 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.

Rx ONLYManufactured 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 or 603-778-6929US Patents 6,696,430 and 6,372,449Copyright (C), 2009 Dutch Ophthalmic Research Center.

STORAGE AND HANDLING SECTION.

MembraneBlue 0.15% Storage and handling section.. MembraneBlue(TM) 0.15% is stored at 15 25C (59 77F). Protect from direct sunlight.

USE IN SPECIFIC POPULATIONS SECTION.

MembraneBlue 0.15% Use in specific populations section. Trypan blue should not be given to pregnant women.. MembraneBlue 0.15% 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 4,000- and 2,000-fold the maximum recommended human dose of 0.75 mg per injection based on 60 kg person, assuming that the whole dose is completely absorved. 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 the 20th to 25th days of pregnancy, but no apparent increase in birth defects (approximately 4,000-fold maximum recommended human dose of 0.75 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.. MembraneBlue 0.15% 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.. MembraneBlue 0.15% 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.. MembraneBlue 0.15% Geriatric use.. No overall differences in safety and effectiveness have been observed between elderly and younger patients.

WARNINGS AND PRECAUTIONS SECTION.

MembraneBlue 0.15% Warnings and precautions section. Excessive staining:It is recommended that after inection all excess MembraneBlue(TM) 0.15% be immediately removed from the eye.Priming of the syringe:Make sure the plunger moves smoothly before use: first retract the plunger or twist the plunger in clockwise motion before injecting the fluid.. Excessive staining: Excess MembraneBlue(TM) 0.15% should be removed from the eye immediately after staining.Priming of the syringe: make sure the plunger moves smoothly before use: first retract the plunger or twist the plunger in clockwise motion before injecting the fluid.. Excessive staining: Excess MembraneBlue(TM) 0.15% should be removed from the eye immediately after staining.. Priming of the syringe: make sure the plunger moves smoothly before use: first retract the plunger or twist the plunger in clockwise motion before injecting the fluid.