MEMBRANEBLUE

MembraneBlue 0.15% - Indications & Usage Section MembraneBlue™ 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™ safely and effectively. See full prescribing information for MEMBRANEBLUE. MEMBRANEBLUE (trypan blue ophthalmic solution) 0.15%, for intraocular ophthalmic use Initial U.S. Approval: 2004 MembraneBlue is a 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

MembraneBlue 0.15% - Dosage & administration section MembraneBlue 0.15% is packaged in a single-patient-use syringe filled to a 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 a clockwise motion until tight. Once tight, continue turning the plunger in a 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 a “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 a 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 a 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 a “fluid-air exchange” (i.e., fill the entire vitreous cavity with air). Carefully apply MembraneBlue to epiretinal membranes using a blunt cannula and remove all excess dye. OR Inject MembraneBlue directly in a BSS filled-vitreous cavity. Wait 30 seconds and remove all excess dye. (2)

MembraneBlue 0.15% - Contraindications section. MembraneBlue 0.15% is contraindicated when a 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 a non-hydrated (dry state), hydrophilic acrylic intraocular lens (IOL). MembraneBlue may be absorbed by the IOL and stain it.

MembraneBlue 0.15% - Warnings and precautions section 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 a 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 a clockwise motion before injecting the fluid.

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.

MembraneBlue - Pregnancy section Risk Summary There are no available data on the use of MembraneBlue 0.15% in pregnant women to inform a 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. Data Animal Data 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 a 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 a 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).