TISSUEBLUE- brilliant blue g injection, solution

TISSUEBLUE by

Drug Labeling and Warnings

TISSUEBLUE by is a Prescription medication manufactured, distributed, or labeled by D.O.R.C. Dutch Ophthalmic Research Center (International) B.V., Pharmpur GmbH. Drug facts, warnings, and ingredients follow.

Drug Details [pdf]

• HIGHLIGHTS OF PRESCRIBING INFORMATION

  These highlights do not include all the information needed to use TissueBlue 0.025% safely and effectively. See full prescribing information for TissueBlue 0.025%.  Initial U.S. Approval: 2019

  INDICATIONS AND USAGE

  TissueBlue (Brilliant Blue G Ophthalmic Solution) 0.025% is is a disclosing agent indicated to selectively stain the internal limiting membrane (ILM). (1)

  DOSAGE AND ADMINISTRATION

  • Inject TissueBlue 0.025% directly in a Balanced Salt Solution (BSS)-filled vitreous cavity. 
  • Excess TissueBlue should be removed from the vitreous cavity.

  DOSAGE FORMS AND STRENGTHS

  TissueBlue (Brilliant Blue G Ophthalmic Solution) 0.025% is supplied in 2.25 mL syringes filled to a volume of 0.5 mL. (3)

  CONTRAINDICATIONS

  None (4)

  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.  (5)

  ADVERSE REACTIONS

  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. (6)

  To report SUSPECTED ADVERSE REACTIONS, contact Dutch Ophthalnic, USA at 1-800-75-DUTCH or FDA at
  1-800-FDA-1088 or www.fda.gov/medwatch (6)

  Revised: 12/2019

• Table of Contents

  FULL PRESCRIBING INFORMATION: CONTENTS*

  TissueBlue 0.025% - Indications & Usage Section

  TissueBlue 0.025% - Dosage & Administration Section

  TissueBlue 0.025% - Dosage forms & Strengths section

  TissueBlue 0.025% - Contraindications section

  TissueBlue 0.025% - Warnings and Precautions section

  TissueBlue 0.025% - Adverse Reactions section

  TissueBlue 0.025% - Use in specific populations section

  TissueBlue 0.025% - Pregnancy section

  TissueBlue 0.025% - Lactation section

  TissueBlue 0.025% - Pediatric use section

  TissueBlue 0.025% - Geriatric use section

  TissueBlue 0.025% - Description section

  TissueBlue 0.025% - Clinical Pharmacology section

  TissueBlue 0.025% - Mechanism of action section

  TissueBlue 0.025% - Nonclinical toxicology section

  TissueBlue 0.025% - Nonclinical toxicology section

  TissueBlue 0.025% - How supplied section

  * Sections or subsections omitted from the full prescribing information are not listed.

TissueBlue 0.025% - Indications & Usage Section

TissueBlue (Brilliant Blue G Ophthalmic Solution) 0.025% is is a disclosing agent indicated to selectively stain the internal limiting membrane (ILM).

TissueBlue 0.025% - Dosage & Administration Section

TissueBlue 0.025% is carefully injected into the Balanced Salt Solution (BSS)-filled vitreous cavity using a 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 a few seconds. Following staining, all excess dye should be removed from the vitreous cavity.

TissueBlue 0.025% - Dosage forms & Strengths section

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

TissueBlue 0.025% - Contraindications section

None

TissueBlue 0.025% - Warnings and Precautions section

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.

TissueBlue 0.025% - Adverse Reactions section

Adverse reactions that have been reported in procedures that included the use of Brilliant Blue G Ophthalmic Solution have often been associated with the surgical procedure. These complications include retinal (retinal break, tear, hemorrhage, and detachment) and cataracts.

TissueBlue 0.025% - Use in specific populations section

TissueBlue 0.025% - Pregnancy section

Risk Summary
There are no available data on the use of TissueBlue 0.025% in pregnant women to inform a 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%.

TissueBlue 0.025% - Lactation section

Risk Summary
No data are available regarding the presence of Brilliant Blue G 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 G 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.

TissueBlue 0.025% - Pediatric use section

The safety and effectiveness of TissueBlue 0.025% in pediatric patients has not been established.

TissueBlue 0.025% - Geriatric use section

No overall differences in safety or effectiveness were observed between elderly and younger adult patients.

TissueBlue 0.025% - Description section

TissueBlue (Brilliant Blue G Ophthalmic Solution) 0.025% is a sterile solution of BBG (a dye). Each mL of TissueBlue 0.025% contains BBG 0.25 mg, Polyethylene Glycol 40mg and Buffered Sodium Chloride solution (8.20 mg of sodium chloride, 3.10 mg sodium phosphate dibasic dodecahydrate, 0.30 mg sodium phosphate monobasic dihydrate, water for injection). 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, a molecular weight of 854.02 and has the following chemical structure:

Molecular formula: C47H48N3NaO7S2

TissueBlue 0.025% - Clinical Pharmacology section

TissueBlue 0.025% - Mechanism of action section

Brilliant Blue G 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.

TissueBlue 0.025% - Nonclinical toxicology section

TissueBlue 0.025% - Nonclinical toxicology section

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

TissueBlue 0.025% - How supplied section

TissueBlue (Brilliant Blue G Ophthalmic Solution), 0.025% is supplied as 0.5 mL of Brilliant Blue G Ophthalmic Solution, 0.025% in a sterile, single-dose Luer Lok, 2.25 mL glass syringe, with a grey rubber plunger stopper and tip cap with polypropylene plunger rod in a pre-formed polypropylene blister pouch sealed with a Tyvek® lid.

NDC: 68803-722-05 (One 0.5 mL syringe)
NDC: 68803-722-25 (Carton of five 0.5 mL syringes)

TissueBlue 0.025% - Storage and Handling section

TissueBlue 0.025% should be stored at 15°C to 25°C (59°F to 77°F). Protect from light, frost and moisture.

SPL UNCLASSIFIED SECTION

Rx Only

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

Revision Date: 12/2019
Made in Germany
All trademarks are the property of their respective owners.

Package Label - 0.5 mL

TissueBlue 

(Brilliant Blue G Ophthalmic Solution) 0.025%

Staining Solution for Ophthalmic Surgery

Protect from light, frost and moisture. Store at 15°C to 25°C (59°F to 77°F). Sterile.

Active ingredients/Ingrédient actif: Brilliant Blue G 0.025% Inactive ingredients/Ingrédients inactifs: Water for injection, Sodium chloride, Sodium phosphate dibasic dihydrate, Sodium phosphate monobasic dihydrate, Polyethylene Glycol.

NDC: 68803-722-05 (One 0.5 mL syringe)
NDC: 68803-722-25 (Carton of five 0.5 mL syringes)

INGREDIENTS AND APPEARANCE

TISSUEBLUE 
brilliant blue g injection, solution

Product Information
Product Type	HUMAN PRESCRIPTION DRUG	Item Code (Source)	NDC: 68803-722
Route of Administration	INTRAOCULAR, OPHTHALMIC

Active Ingredient/Active Moiety
Ingredient Name	Basis of Strength	Strength
BRILLIANT BLUE G (UNII: M1ZRX790SI) (BRILLIANT BLUE G - UNII:M1ZRX790SI)	BRILLIANT BLUE G	0.0125 mg  in 0.5 mL

Inactive Ingredients
Ingredient Name	Strength
POLYETHYLENE GLYCOL 3350 (UNII: G2M7P15E5P)	2 mg  in 0.5 mL
SODIUM CHLORIDE (UNII: 451W47IQ8X)	8.2 mg  in 0.5 mL
SODIUM PHOSPHATE, DIBASIC, DODECAHYDRATE (UNII: E1W4N241FO)	3.1 mg  in 0.5 mL
SODIUM PHOSPHATE, MONOBASIC, DIHYDRATE (UNII: 5QWK665956)	0.3 mg  in 0.5 mL
WATER (UNII: 059QF0KO0R)	4743 g  in 0.5 mL

Packaging
#	Item Code	Package Description	Marketing Start Date	Marketing End Date
1	NDC: 68803-722-05	10 in 1 CARTON	12/31/2019
1		1 in 1 POUCH
1		0.5 mL in 1 SYRINGE, GLASS; Type 2: Prefilled Drug Delivery Device/System (syringe, patch, etc.)

Marketing Information
Marketing Category	Application Number or Monograph Citation	Marketing Start Date	Marketing End Date
NDA	NDA209569	12/31/2019

Labeler - D.O.R.C. Dutch Ophthalmic Research Center (International) B.V. (407522184)

Registrant - D.O.R.C. Dutch Ophthalmic Research Center (International) B.V. (407522184)

Establishment
Name	Address	ID/FEI	Business Operations
Pharmpur GmbH		340805167	manufacture(68803-722)