PREGNANCY SECTION.

Pregnancy. Risk Summary There are no available data on the use of TissueBlue 0.025% in pregnant women to inform drug associated risk. Systemic absorption of TissueBlue 0.025% in humans is expected to be negligible following intravitreal injection and subsequent removal of the drug at the completion of surgical procedures. Due to the negligible systemic exposure, it is not expected that maternal use of TissueBlue 0.025% will result in fetal exposure to the drug. Adequate animal reproduction studies were not conducted with TissueBlue 0.025%.

SPL UNCLASSIFIED SECTION.

Manufactured for D.O.R.C., Dutch Ophthalmic Research Center (International) B.V., Zuidland, 3214 VN, The NetherlandsMade in GermanyAll trademarks are the property of their respective owners.

ADVERSE REACTIONS SECTION.

Adverse Reactions Adverse reactions that have been reported in procedures that included the use of Brilliant Blue Ophthalmic Solution have often been associated with the surgical procedure. These complications include retinal (retinal break, tear, hemorrhage, and detachment) and cataracts.. Adverse reactions that have been reported in procedures that included the use of TissueBlue 0.025% have often been associated with the surgical procedure. The complications include retinal (retinal break, tear, hemorrhage, and detachment and cataracts.To report SUSPECTED ADVERSE REACTIONS, contact Dutch Ophthalmic, USA at 1-800-75-DUTCH or FDA at1-800-FDA-1088 or www.fda.gov/medwatch.

CLINICAL PHARMACOLOGY SECTION.

Clinical Pharmacology. Mechanism of action. Brilliant Blue has been shown to selectively stain the ILM, but not the epiretinal membrane nor the retina, making it easier to visualize the membrane for removal, although the exact mechanism of this selectivity has not been elucidated.

DESCRIPTION SECTION.

Description. TissueBlue (Brilliant Blue Ophthalmic Solution) 0.025% is sterile solution of BBG (a dye) for intraocular ophthalmic use. Each mL of TissueBlue 0.025% contains BBG 0.25 mg, polyethylene glycol and buffered sodium chloride solution (sodium chloride, dibasic sodium phosphate, monobasic sodium phospage, water for injection). Phosphoric acid and/or sodium hydroxide may also be used for pH adjustment. The pH range of TissueBlue 0.025% Solution is between 7.3 and 7.6. The drug substance BBG has the chemical name Brilliant Blue G, molecular weight of 854.02 and has the following chemical structure: Molecular formula: 47H 48N 3NaO 7S . BBG.jpg.

DOSAGE & ADMINISTRATION SECTION.

Dosage Administration TissueBlue 0.025% is carefully injected into the Balanced Salt Solution (BSS)-filled vitreous cavity using blunt cannula attached to the pre-filled syringe, without allowing the cannula to contact the retina or allowing TissueBlue to get under the retina. Sufficient staining is expected within few seconds. Following staining, all excess dye should be removed from the vitreous cavity.. Inject TissueBlue 0.025% directly in Balanced Salt Solution (BSS)-filled vitreous cavity. Excess TissueBlue should be removed from the vitreous cavity.. Inject TissueBlue 0.025% directly in Balanced Salt Solution (BSS)-filled vitreous cavity. Excess TissueBlue should be removed from the vitreous cavity.

DOSAGE FORMS & STRENGTHS SECTION.

Dosage forms Strengths TissueBlue (Brilliant Blue Ophthalmic Solution) 0.025% is clear, bright blue, single-dose ophthalmic solution supplied in 2.25 mL syringes pre-filled to volume of 0.5 mL.. TissueBlue (Brilliant Blue Ophthalmic Solution) 0.025% is supplied in 2.25 mL syringes filled to volume of 0.5 mL.

HOW SUPPLIED SECTION.

How Supplied/Storage and Handling. TissueBlue (Brilliant Blue Ophthalmic Solution), 0.025% is supplied as 0.5 mL of Brilliant Blue Ophthalmic Solution, 0.025% in sterile, single-dose Luer Lok, 2.25 mL glass syringe, with grey rubber plunger stopper and tip cap with polypropylene plunger rod in pre-formed polypropylene blister pouch sealed with Tyvek(R) lid. NDC 68803-722-05 (One 0.5 mL syringe) NDC 68803-722-25 (Carton of five 0.5 mL syringes).

INDICATIONS & USAGE SECTION.

Indications Usage. TissueBlue 0.025% is indicated to selectively stain the internal limiting membrane (ILM).. TissueBlue 0.025% is disclosing agent indicated to selectively stain the internal limiting membrane (ILM).

LACTATION SECTION.

Lactation. Risk Summary No data are available regarding the presence of Brilliant Blue in human milk after intraocular administration of TissueBlue 0.025%, or the effects on the breastfed infant or the effects on milk production. However, breastfeeding is not expected to result in exposure of the child to Brilliant Blue due to the expected negligible systemic exposure of BBG in humans following intravitreal injection and subsequent removal of the drug at the completion of surgical procedures.

MECHANISM OF ACTION SECTION.

Mechanism of action. Brilliant Blue has been shown to selectively stain the ILM, but not the epiretinal membrane nor the retina, making it easier to visualize the membrane for removal, although the exact mechanism of this selectivity has not been elucidated.

NONCLINICAL TOXICOLOGY SECTION.

Nonclinical toxicology. Nonclinical toxicology. Studies to evaluate the potential for carcinogenicity or impairment of fertility of TissueBlue 0.025% have not been conducted. Brilliant Blue was not mutagenic in the Ames assay, the in vitro mouse lymphoma assay, or the in vivo rat micronucleus assay.

PACKAGE LABEL.PRINCIPAL DISPLAY PANEL.

Package Label 0.5 mL. TissueBlue(Brilliant Blue Ophthalmic Solution) 0.025%Staining Solution for Ophthalmic SurgeryProtect from light, frost and moisture. Store at 15C to 25C (59F to 77F). Sterile.Active ingredients: Brilliant Blue 0.025% Inactive ingredients: Water for injection, Sodium chloride, dibasic sodium phosphate, monobasic sodium phosphate, polyethylene glycol, phosphoric acid and/or sodium hydroxide may also be used for pH adjustment.NDC 68803-722-05 (One 0.5 mL syringe) NDC 68803-722-25 (Carton of five 0.5 mL syringes) carton.jpg.

USE IN SPECIFIC POPULATIONS SECTION.

Use in specific populations Pregnancy. Risk Summary There are no available data on the use of TissueBlue 0.025% in pregnant women to inform drug associated risk. Systemic absorption of TissueBlue 0.025% in humans is expected to be negligible following intravitreal injection and subsequent removal of the drug at the completion of surgical procedures. Due to the negligible systemic exposure, it is not expected that maternal use of TissueBlue 0.025% will result in fetal exposure to the drug. Adequate animal reproduction studies were not conducted with TissueBlue 0.025%. Lactation. Risk Summary No data are available regarding the presence of Brilliant Blue in human milk after intraocular administration of TissueBlue 0.025%, or the effects on the breastfed infant or the effects on milk production. However, breastfeeding is not expected to result in exposure of the child to Brilliant Blue due to the expected negligible systemic exposure of BBG in humans following intravitreal injection and subsequent removal of the drug at the completion of surgical procedures. Pediatric use. The safety and effectiveness of TissueBlue 0.025% in pediatric patients has not been established.. Geriatric use. No overall differences in safety or effectiveness were observed between elderly and younger adult patients.

WARNINGS AND PRECAUTIONS SECTION.

Warnings and Precautions Excessive Staining Excess TissueBlue 0.025% should be removed from the eye immediately after staining. Use of the Syringe Make sure the plunger moves smoothly before injecting the solution. Do not use the product if the plunger does not move smoothly to prime the cannula. Excessive staining: Excess TissueBlue 0.025% should be removed from the eye immediately after staining. Use of the syringe: Make sure the plunger moves smoothly before injecting the solution.