Indocyanine Green

1 INDICATIONS AND USAGE Indocyanine Green for injection is indicated: Indocyanine Green for injection is an optical imaging agent indicated for: • Fluorescence imaging of vessels (micro- and macro-vasculature), blood flow and tissue perfusion before, during and after vascular, gastrointestinal, organ transplant, plastic, micro- and reconstructive surgeries, including general minimally invasive surgical procedures, in adults and pediatric patients aged 1 month and older ( 1.1 ) • Fluorescence imaging of extrahepatic biliary ducts in adults and pediatric patients aged 12 years and older ( 1.2 ) • Fluorescence imaging of lymph nodes and lymphatic vessels during lymphatic mapping in adults with cervical and uterine cancer ( 1.3 ) • Ophthalmic angiography in adults and pediatric patients ( 1.4 ) 1.1 Visualization of Vessels, Blood Flow and Tissue Perfusion Indocyanine Green is indicated for fluorescence imaging of vessels (micro- and macro- vasculature), blood flow and tissue perfusion before, during and after vascular, gastrointestinal, organ transplant, plastic, micro- and reconstructive surgeries, including general minimally invasive surgical procedures in adults and pediatric patients aged 1 month and older. 1.2 Visualization of Extrahepatic Biliary Ducts Indocyanine Green is indicated for fluorescence imaging of extrahepatic biliary ducts in adults and pediatric patients aged 12 years and older . 1.3 Lymphatic Mapping of Cervical and Uterine Cancer Indocyanine Green is indicated for fluorescence imaging of lymph nodes and delineation of lymphatic vessels during lymphatic mapping in adults with cervical and uterine cancer for which this procedure is a component of intraoperative management. 1.4 Ophthalmic Angiography Indocyanine Green is indicated for use in ophthalmic angiography in adults and pediatric patients.

2 DOSAGE AND ADMINISTRATION • Visualization of vessels, blood flow and tissue perfusion (2.5 mg/mL solution) o 1.25 mg to 5 mg by intravenous injection is recommended for a surgical procedure in adults and pediatric patients aged 1 month and older. o 3.75 mg to 10 mg by intravenous injection is recommended for visualization of perfusion in extremities through the skin for plastic, micro- and reconstructive surgeries in adults. o Additional doses may be administered. Do not exceed a total dose of 2 mg/kg. ( 2.1 ) • Visualization of extrahepatic biliary ducts in adults and pediatric patients aged 12 years and older (2.5 mg/mL solution) o 2.5 mg by intravenous injection at least 45 minutes prior to surgery. o Additional doses may be administered. Do not exceed a total dose of 2 mg/kg. ( 2.2 ) • Lymphatic mapping of cervical and uterine cancer in adults (1.25 mg/mL solution) o 5 mg interstitially as four 1 mL injections. o See Full Prescribing Information for injection techniques. ( 2.3 ) • Ophthalmic Angiography o Doses up to 40 mg in 2 ml of Sterile Water for Injection by intravenous injection. ( 2.4 ) • See Full Prescribing Information for reconstitution instructions. ( 2.5 ). 2.1 Indicator-Dilution Studies Dosing Adults: The recommended dose of Indocyanine Green for a single image sequence for visualization of vessels, blood flow and tissue perfusion in adults is 1.25 mg to 5 mg administered intravenously as 0.5 mL to 2 mL of a 2.5 mg/mL solution. For visualization of perfusion in extremities through the skin in adults, the recommended dose is 3.75 mg to 10 mg administered intravenously as 1.5 mL to 4 mL of a 2.5 mg/mL solution. Immediately flush with a 10 mL bolus of 0.9% Sodium Chloride Injection. Pediatric patients aged 1 month and older: The recommended dose of Indocyanine Green for a single image sequence for visualization of vessels, blood flow and tissue perfusion in pediatric patients aged 1 month and older is 1.25 mg to 5 mg administered intravenously as 0.5 mL to 2 mL of a 2.5 mg/mL solution. Lower doses may be administered in younger patients and in those with lower body weight. Adjust the amount and type of flush to avoid volume and/or sodium overload. In both adults and pediatric patients aged 1 month and older, additional doses may be administered to obtain imaging sequences during the procedure. Do not exceed the maximum total dose of 2 mg/kg. Administration Prior to the imaging procedure, draw up the desired dose of Indocyanine Green solution into appropriate syringes and prepare a 10 mL syringe of 0.9% Sodium Chloride Injection. Administer via a central or peripheral venous line using a three-way stopcock attached to an injection port on the infusion line. Inject the prepared Indocyanine Green into the line as a tight bolus. Immediately switch the access on the stopcock and inject the prepared flush. Imaging Instructions Indocyanine Green may be used with an FDA-authorized imaging device that is intended to be used with indocyanine green for fluorescence imaging of vessels, blood flow and tissue perfusion. A fluorescence response should be visible in blood vessels within 5 seconds to 15 seconds after injection. 2.2 Recommended Dose, Administration and Imaging for Visualization of Extrahepatic Biliary Ducts Dosing and Administration The recommended dose of Indocyanine Green for visualization of extrahepatic biliary ducts in adults and pediatric patients aged 12 years and older is 2.5 mg administered intravenously as 1 mL of a 2.5 mg/mL solution at least 45 minutes prior to surgery. Additional doses may be administered to obtain imaging sequences during the procedure. Do not exceed a total dose of 2 mg/kg. Imaging Instructions Indocyanine Green may be used with an FDA-authorized imaging device that is intended to be used with indocyanine green for fluorescence imaging of extrahepatic biliary ducts. Fluorescence is visible in the biliary tree within 45 minutes after injection. 2.3 Recommended Dose, Administration and Imaging for Lymphatic Mapping of Cervical and Uterine Cancer Dosing and Administration The recommended dose of Indocyanine Green for lymphatic mapping of cervical and uterine cancer in adults is 5 mg administered interstitially as four 1 mL injections of a 1.25 mg/mL solution into the cervix, at the 3 o’ clock and the 9 o’clock positions with a superficial (1 mm to 3 mm) and a deep (1 cm to 3 cm) injection at each position. Imaging Instructions Indocyanine Green may be used with an FDA-authorized imaging device that is intended to be used with indocyanine green for fluorescence imaging of lymph nodes and delineation of lymphatic vessels during lymphatic mapping of cervical and uterine cancer. Fluorescent lymphatic vessels and lymph nodes should begin to be visible within 1 minute after injection. 2.4 Recommended Dose and Administration for Ophthalmic Angiography Dosing and Administration Doses up to 40 mg Indocyanine Green in 2 mL of Sterile Water for Injection depending on the imaging equipment and technique used should be administered intravenously and immediately followed by a 5 mL bolus of 0.9% Sodium Chloride Injection. The antecubital vein can be used for Indocyanine Green administration. 2.5 Reconstitution Instructions General • Prepare Indocyanine Green for injection using aseptic techniques prior to procedure. • Inspect the reconstituted solution for particulate matter. The reconstituted solution should be a clear, green solution. • Use the prepared solution within 6 hours. • Discard any unused product. Visualization of Vessels, Blood Flow, Tissue Perfusion and Extrahepatic Biliary Ducts Dissolve 25 mg of Indocyanine Green with 10 mL Sterile Water for Injection to form a concentration of 2.5 mg/mL indocyanine green. Lymphatic Mapping of Cervical and Uterine Cancer Dissolve 25 mg of Indocyanine Green with 20 mL Sterile Water for Injection to form a concentration of 1.25 mg/mL indocyanine green. Ophthalmic Angiography Dissolve doses up to 40 mg of Indocyanine Green with 2 mL Sterile Water for Injection.

4 CONTRAINDICATIONS Indocyanine Green is contraindicated in patients with a history of hypersensitivity to indocyanine green. Reactions have included anaphylaxis [see Warnings and Precautions ( 5.1 )] . Hypersensitivity to indocyanine green ( 4 )

5 WARNINGS AND PRECAUTIONS Hypersensitivity reactions: Hypersensitivity reactions including anaphylaxis and urticaria have occurred. Always have cardiopulmonary resuscitation personnel and equipment readily available and monitor patients. ( 5.1 ) 5.1 Hypersensitivity Reactions Hypersensitivity reactions including anaphylaxis, urticaria and deaths due to anaphylaxis have been reported following intravenous administration of Indocyanine Green [see Adverse Reactions ( 6 )]. Indocyanine Green is contraindicated in patients with a history of hypersensitivity to indocyanine green [see Contraindications ( 4 )] . Always have cardiopulmonary resuscitation personnel and equipment readily available and monitor all patients for hypersensitivity reactions. 5.2 Interference with Thyroid Radioactive Iodine Uptake Studies Because Indocyanine Green contains sodium iodide, the iodine-binding capacity of thyroid tissue may be reduced for at least one week following administration [see Drug Interactions ( 7 )].

7 DRUG INTERACTIONS Interference with Thyroid Radioactive Iodine Uptake Studies Because Indocyanine Green contains sodium iodide, the iodine-binding capacity of thyroid tissue may be reduced for at least one week following administration. Do not perform radioactive iodine uptake studies for at least one week following administration of Indocyanine Green. Interference with Thyroid Radioactive Iodine Uptake Studies: Do not perform radioactive iodine uptake studies for at least one week following the use of Indocyanine Green. ( 7 )

6 ADVERSE REACTIONS The following clinically significant adverse reactions are described elsewhere in the labeling: • Hypersensitivity Reactions [see Warnings and Precautions ( 5.1 )] . The following adverse reactions have been identified during post-approval use of Indocyanine Green. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Immune System Disorders : Anaphylaxis, urticaria The most common adverse reactions reported are anaphylaxis and urticaria. ( 6 ) To report SUSPECTED ADVERSE REACTIONS, contact Diagnostic Green LLC at 1-844-424-3784 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

8.1 Pregnancy Risk Summary There are no adequate and well-controlled studies of Indocyanine Green in pregnant women. Available data from a very small number of scientific literature studies with indocyanine green use in pregnant women over several decades have not reported any drug associated risks for major birth defects, miscarriage, or adverse maternal or fetal outcomes. Data from one small study in which indocyanine green was administered intravenously to pregnant women during labor suggest there is no placental transfer of the drug. Animal reproduction studies have not been conducted with indocyanine green. All pregnancies have a background risk of birth defects, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively.