HOW SUPPLIED SECTION.

MembraneBlue How supplied section. MembraneBlue (trypan blue ophthalmic solution) 0.15% is clear, dark blue ophthalmic solution supplied as follows:0.5 mL of MembraneBlue 0.15% in sterile single-patient-use Luer Lock, 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.NDC 68803-672-01 (One 0.5 mL syringe) NDC 68803-672-05 (Carton of five 0.5 mL syringes).

DOSAGE FORMS & STRENGTHS SECTION.

MembraneBlue 0.15% Dosage forms strengths section.. MembraneBlue (trypan blue ophthalmic solution) 0.15% is clear, dark blue ophthalmic solution supplied in 2.25 mL single-patient-use syringe filled to volume of 0.5 mL.. Ophthalmic solution: 0.15% trypan blue in single-patient-use syringe.

ADVERSE REACTIONS SECTION.

MembraneBlue 0.15% Adverse reactions section. Adverse reactions reported following use of MembraneBlue 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.. Most common adverse reactions include discoloration of high water content hydrogen intraocular lenses and 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.

CLINICAL PHARMACOLOGY SECTION.

MembraneBlue Clinical Pharmacology Section. MembraneBlue 0.15% Mechanism of action section.. MembraneBlue 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 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). MembraneBlue may be absorbed by the IOL and stain it.

DESCRIPTION SECTION.

MembraneBlue Description.. MembraneBlue(TM) (trypan blue ophthalmic solution) 0.15% is sterile solution of trypan blue (an acid di-azo group dye) for intraocular ophthalmic use. MembraneBlue selectively stains epiretinal membranes during ophthalmic surgical vitrectomy procedures.Each mL of MembraneBlue 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. MembraneBlue 0.15% is packaged in single-patient-use syringe filled to volume of 0.5 mL. 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 perform fluid-air exchange (i.e., filling the entire vitreous cavity with air, to prevent aqueous dilution of MembraneBlue). MembraneBlue is carefully applied to the retinal membrane using blunt cannula attached to the MembraneBlue 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 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 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, perform fluid-air exchange (i.e., fill the entire vitreous cavity with air). Carefully apply MembraneBlue to epiretinal membranes using blunt cannula and remove all excess dye. OR Inject MembraneBlue directly in BSS filled-vitreous cavity. Wait 30 seconds and remove all excess dye. (2). Prior to injection of MembraneBlue, perform fluid-air exchange (i.e., fill the entire vitreous cavity with air). Carefully apply MembraneBlue to epiretinal membranes using blunt cannula and remove all excess dye. OR Inject MembraneBlue directly in BSS filled-vitreous cavity. Wait 30 seconds and remove all excess dye. (2).

GERIATRIC USE SECTION.

MembraneBlue Geriatric use. No overall differences in safety and effectiveness were observed between elderly and younger patients.

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 in adults and pediatric patients.. These highlights do not include all the information needed to use MEMBRANEBLUE(TM) safely and effectively. See full prescribing information for MEMBRANEBLUE. MEMBRANEBLUE (trypan blue ophthalmic solution) 0.15%, for intraocular ophthalmic use Initial U.S. Approval: 2004MembraneBlue is diagnostic dye indicated for use as an aid in ophthalmic posterior surgery by staining the epiretinal membranes during ophthalmic surgical vitrectomy procedures, facilitating removal of epiretinal tissue in adults and pediatric patients.

MECHANISM OF ACTION SECTION.

MembraneBlue 0.15% Mechanism of action section.. MembraneBlue 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 Nonclinical toxicology section. Carinogenesis, Mutagenesis, Impairment of FertilityCarcinogenesisTrypan 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 (approximately 645-fold the maximum recommended human dose of 0.75 mg per injection in 60 kg person based on BSA, assuming complete systemic absorption).Mutagenesis Trypan blue was mutagenic in the Ames test and caused DNA strand breaks in vitro.

NURSING MOTHERS SECTION.

MembraneBlue Lactation section. Risk Summary The presence of trypan blue in human milk following intraocular administration of trypan blue has not been evaluated. There are no data available regarding the effects of trypan blue on milk production. Breastfeeding is not expected to result in exposure of the child to trypan blue due to the negligible systemic exposure of trypan blue in humans following injection and subsequent removal of the drug at the completion of surgical procedures.

PACKAGE LABEL.PRINCIPAL DISPLAY PANEL.

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

PEDIATRIC USE SECTION.

MembraneBlue 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 Pregnancy section. Risk Summary There are no available data on the use of MembraneBlue 0.15% in pregnant women to inform drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes. Systemic absorption of MembraneBlue 0.15% in humans is expected to be negligible following injection and subsequent removal of the drug at the completion of surgical procedures. Adequate animal reproduction studies were not conducted with MembraneBlue 0.15%, however, trypan blue has been shown to be teratogenic in various animal models at doses 323-fold and greater than the maximum recommended human dose, based on body surface area (BSA). Due to the negligible human systemic exposure when used as recommended, it is not expected that maternal use of MembraneBlue will result in fetal exposure to the drug and risk of teratogenic effects.DataAnimal DataTrypan 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. Normalized to BSA, these doses are approximately 645- and 323-fold the maximum recommended human dose of 0.75 mg per injection (based on 60 kg person), assuming complete systemic absorption of trypan blue. 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 1,300-fold the maximum recommended human dose based on BSA, assuming complete systemic absorption).

SPL UNCLASSIFIED SECTION.

Made in GermanyDistributed in the United States byDutch Ophthalmic, USA10, Continental Drive, Bldg 1Exeter, NH 03833, USAPhone: 800-75-DUTCH or 603-778-6929.

STORAGE AND HANDLING SECTION.

MembraneBlue Storage and handling section. Storage: Store between 15oC to 25oC (59oF to 77oF). Protect from direct sunlight. Single-patient-use. Discard unused portion.

USE IN SPECIFIC POPULATIONS SECTION.

MembraneBlue Use in specific populations section. MembraneBlue should not be given to pregnant women. MembraneBlue Pregnancy section. Risk Summary There are no available data on the use of MembraneBlue 0.15% in pregnant women to inform drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes. Systemic absorption of MembraneBlue 0.15% in humans is expected to be negligible following injection and subsequent removal of the drug at the completion of surgical procedures. Adequate animal reproduction studies were not conducted with MembraneBlue 0.15%, however, trypan blue has been shown to be teratogenic in various animal models at doses 323-fold and greater than the maximum recommended human dose, based on body surface area (BSA). Due to the negligible human systemic exposure when used as recommended, it is not expected that maternal use of MembraneBlue will result in fetal exposure to the drug and risk of teratogenic effects.DataAnimal DataTrypan 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. Normalized to BSA, these doses are approximately 645- and 323-fold the maximum recommended human dose of 0.75 mg per injection (based on 60 kg person), assuming complete systemic absorption of trypan blue. 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 1,300-fold the maximum recommended human dose based on BSA, assuming complete systemic absorption).. MembraneBlue Lactation section. Risk Summary The presence of trypan blue in human milk following intraocular administration of trypan blue has not been evaluated. There are no data available regarding the effects of trypan blue on milk production. Breastfeeding is not expected to result in exposure of the child to trypan blue due to the negligible systemic exposure of trypan blue in humans following injection and subsequent removal of the drug at the completion of surgical procedures. MembraneBlue 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 Geriatric use. No overall differences in safety and effectiveness were observed between elderly and younger patients.

WARNINGS AND PRECAUTIONS SECTION.

MembraneBlue 0.15% Warnings and precautions section. Excessive StainingExcess MembraneBlue 0.15% should be immediately removed from the eye after staining.Priming of the SyringeTo 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 0.15% should be immediately removed from the eye after staining.Priming of the Syringe: To 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 0.15% should be immediately removed from the eye after staining.. Priming of the Syringe: To make sure the plunger moves smoothly before use, first retract the plunger or twist the plunger in clockwise motion before injecting the fluid.