Membraneblue drug information

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

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 - 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 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). 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.

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).

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.

MembraneBlue - Description. MembraneBlue™ (trypan blue ophthalmic solution) 0.15% is a 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 2 HPO 4 •2H 2 O); 0.3 mg sodium di-hydrogen orthophosphate (NaH 2 PO 4 •2H 2 O); 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, a molecular weight of 960.8, a molecular formula of C 34 H 24 N 6 Na 4 O 14 S 4 , and has the following chemical structure: Chemical structure MembraneBlue

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).

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).

MembraneBlue - Nonclinical toxicology section Carinogenesis, Mutagenesis, Impairment of Fertility Carcinogenesis 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 (approximately 645-fold the maximum recommended human dose of 0.75 mg per injection in a 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.

MembraneBlue - How supplied section MembraneBlue (trypan blue ophthalmic solution) 0.15% is a clear, dark blue ophthalmic solution supplied as follows: 0.5 mL of MembraneBlue 0.15% in a sterile single-patient-use Luer Lock, 2.25 mL glass syringe, grey rubber plunger stopper and tip cap with polypropylene plunger rod in a 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)

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

Made in Germany Distributed in the United States by Dutch Ophthalmic, USA 10, Continental Drive, Bldg 1 Exeter, NH 03833, USA Phone: 800-75-DUTCH or 603-778-6929