Isosulfan Blue

Warnings and Precautions, Interference with Oxygen Saturation and Methemoglobin Measurements ( 5.3 ). 10/2007

1 INDICATIONS AND USAGE Isosulfan Blue Injection 1% upon subcutaneous administration, delineates the lymphatic vessels draining the region of injection. It is an adjunct to lymphography in: primary and secondary lymphedema of the extremities; chyluria, chylous ascites or chylothorax; lymph node involvement by primary or secondary neoplasm; lymph node response to therapeutic modalities ( 1.1 ). 1.1 Lymphatic Vessel Delineation Isosulfan Blue Injection 1% upon subcutaneous administration, delineates lymphatic vessels draining the region of injection. It is an adjunct to lymphography in: primary and secondary lymphedema of the extremities; chyluria, chylous ascites or chylothorax; lymph node involvement by primary or secondary neoplasm; and lymph node response to therapeutic modalities.

2 DOSAGE AND ADMINISTRATION Isosulfan blue injection 1% is to be administered subcutaneously, one-half (1/2) mL into three (3) interdigital spaces of each extremity per study. A maximum dose of 3 mL (30 mg) isosulfan blue is, therefore, injected ( 2.1 ). 2.1 Subcutaneous administration Isosulfan blue injection 1% is to be administered subcutaneously, one-half (1/2) mL into three (3) interdigital spaces of each extremity per study. A maximum dose of 3 mL (30 mg) isosulfan blue is, therefore, injected. Discard unused portion. 2.2 Instructions for Preparation and Administration of the 1 mL or 3 mL Pre-filled Syringe To be prepared and administered by a healthcare provider only. For subcutaneous injection only. Do not inject by any other route. As a precaution, always wear gloves. Inspect isosulfan blue injection for particulate matter and discoloration prior to administration. Figure A shows an annotated drawing of the 3 mL syringe. Appearance may differ for the 1 mL syringe. Figure A 1) Grip the syringe at the luer lock collar and remove the tip cap from the prefilled syringe by twisting the cap anticlockwise and pulling upwards ( See Figure B ) Figure B 2) Hold the luer lock collar and attach the needle to the syringe with a firm clockwise twisting motion ( See Figure C ). Figure C 3) Remove the needle sheath with a straight pull. Do not twist the sheath as the needle may become loosened from the syringe ( See Figure D ) Figure D 4) Hold the syringe with the attached needle in an upright position. Prime the syringe by tapping the syringe barrel and moving the plunger stopper carefully forward to the first graduation mark (this may expel air and excess solution) ( See Figure E ) Figure E 5) Administer one-half (1/2) mL subcutaneously, into three (3) interdigital spaces of each extremity per study. 6) Dispose of the used supplies in an approved sharps container in accordance with local hospital procedures. Figure A Figure B Figure C Figure D Figure E

3 DOSAGE FORMS AND STRENGTHS 1% clear dark blue, sterile, non-pyrogenic aqueous solution (isosulfan blue) for subcutaneous administration available as: • 5 mL single-dose vial • 1 mL single-dose pre-filled syringe • 3 mL single-dose pre-filled syringe 1% clear dark blue, sterile, non-pyrogenic aqueous solution (isosulfan blue) for subcutaneous administration available as: ( 3 ) • 5 mL single-dose vial • 1 mL single-dose pre-filled syringe • 3 mL single-dose pre-filled syringe

4 CONTRAINDICATIONS Isosulfan blue injection 1% is contraindicated in those individuals with known hypersensitivity to triphenylmethane or related compounds. Hypersensitivity to triphenylmethane or related compounds ( 4 ).

6 ADVERSE REACTIONS Hypersensitivity Reactions: Hypersensitivity reactions occur in approximately 2% of patients and include life threatening anaphylactic reactions with respiratory distress, shock, angioedema, urticaria, pruritus. A death has been reported following IV administration of a similar compound ( 6 ). To report SUSPECTED ADVERSE REACTIONS, contact Devatis, Inc. at 1-833-534-4406 or druginfo@devatis.com or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Post-Marketing Experience Hypersensitivity Reactions: Case series report an overall incidence of hypersensitivity reactions in approximately 2% of patients. Life threatening anaphylactic reactions have occurred. Manifestations include respiratory distress, shock, angioedema, urticaria, pruritus. A death has been reported following administration of a similar compound employed to estimate the depth of a severe burn. Reactions are more likely to occur in patients with a personal or family history of bronchial asthma, significant allergies, drug reactions or previous reactions to triphenylmethane dyes [see Warnings and Precautions (5) ]. Laboratory Tests: Isosulfan blue injection interferes with measurements of oxygen saturation by pulse oximetry and of methemoglobin by gas analyzer [see Warnings and Precautions (5) ]. Skin: transient or long-term (tattooing) blue coloration.

7 DRUG INTERACTIONS No drug interactions have been identified with isosulfan blue injection 1%. No drug interactions have been identified for isosulfan blue injection 1% ( 7 ).

8 USE IN SPECIFIC POPULATIONS • Caution should be exercised when isosulfan blue injection 1% is administered to nursing mothers ( 8.3 ). • Safety and effectiveness of isosulfan blue injection 1% in children has not been established ( 8.4 ). 8.3 Nursing Mothers It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when isosulfan blue injection 1% is administered to a nursing mother. 8.4 Pediatric Use Safety and effectiveness of isosulfan blue injection 1% in children have not been established.

11 DESCRIPTION The chemical name of isosulfan blue injection 1% is N-[4- [[4-(diethylamino)phenyl] (2,5-disulfophenyl) methylene]-2,5-cyclohexadien-1-ylidene]-N-ethylethanaminium hydroxide, inner salt, sodium salt. Its structural formula is: ISOSULFAN BLUE Isosulfan blue injection 1% is a clear dark blue, sterile, non-pyrogenic aqueous solution for subcutaneous administration. Phosphate buffer in sterile, pyrogen free water is added in sufficient quantity to yield a final pH of 6.8 to 7.4. Each mL of solution contains 10 mg isosulfan blue, 6.6 mg sodium monohydrogen phosphate and 2.7 mg potassium dihydrogen phosphate. Each mL of isosulfan blue injection contains 2 mg of sodium and less than 5 mg of phosphorus. The solution contains no preservative. Isosulfan blue injection 1% is a contrast agent for the delineation of lymphatic vessels. Chemical Structure

10 OVERDOSAGE Do not exceed indicated recommended dosage as overdosage levels have not been identified for isosulfan blue injection 1%.

16 HOW SUPPLIED/STORAGE AND HANDLING Isosulfan Blue Injection 1% is supplied as a 5 mL single-dose vial, 1 mL and 3 mL pre-filled syringe containing 1% clear dark blue, aqueous solution in a phosphate buffer prepared by appropriate manufacturing to be sterile and pyrogen-free. NDC 67457-220-05 50 mg/5 mL (10 mg/mL) carton containing 6 x 5 mL single-dose vials NDC 72078-069-01 10 mg/mL carton containing 1 x 1 mL pre-filled syringe NDC 72078-070-03 30 mg/3 mL (10 mg/mL) carton containing 1 x 3 mL pre-filled syringe Storage: Store at 20° to 25°C (68° to 77°F). [See USP Controlled Room Temperature.] Avoid excessive heat. Discard unused portion.