{"carcinogenesis_and_mutagenesis_and_impairment_of_fertility":["13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility No studies have been performed to evaluate the potential for carcinogenicity, mutagenicity, or impairment of fertility by indocyanine green."],"clinical_pharmacology":["12 CLINICAL PHARMACOLOGY 12.1 Mechanism of Action When bound to proteins in plasma or in lymph fluid, indocyanine green absorbs light in the near-infrared region with peak absorption at 805 nm and emits fluorescence (light) at a slightly longer wavelength, with peak emission at 830 nm. Fluorescence imaging devices provide external energy as near infrared light for indocyanine green to absorb, resulting in excitation of the indocyanine green, and the emitted light (fluorescence) is transferred from the field of view to an image on a monitor. These optical properties of indocyanine green are utilized in fluorescence imaging of the micro- and macro-vasculature, blood flow and tissue perfusion, the extrahepatic biliary ducts, and for lymphatic mapping of lymph nodes and lymphatic vessels. 12.2 Pharmacodynamics There are no pharmacodynamic data. 12.3 Pharmacokinetics Distribution Following intravenous injection, indocyanine green binds to plasma proteins (98%) and is largely confined to the intravascular compartment. Indocyanine green undergoes no significant extrahepatic or enterohepatic circulation; simultaneous arterial and venous blood estimations have shown negligible renal, peripheral, lung or cerebro-spinal uptake of the dye. After biliary obstruction, the dye appears in the hepatic lymph, independently of the bile, suggesting that the biliary mucosa is sufficiently intact to prevent diffusion of the dye, though allowing diffusion of bilirubin. Following interstitial injection, indocyanine green binds to proteins in lymph fluid and the interstitial space, is taken up by the lymphatic vessels, and drains to the lymph nodes. Since excessive dye extravasation does not take place in the highly fenestrated choroidal vasculature, Indocyanine Green is useful in both absorption and fluorescence infrared angiography of the choroidal vasculature when using appropriate filters and film in a fundus camera. Elimination Indocyanine green is taken up from the plasma almost exclusively by the hepatic parenchymal cells and is secreted entirely into the bile."],"clinical_studies":["14 CLINICAL STUDIES 14.1 Lymphatic Mapping of Cervical and Uterine Cancer The effectiveness of Indocyanine Green for fluorescence imaging of lymph nodes and delineation of lymphatic vessels during lymphatic mapping in adults with cervical and uterine cancer has been established based on a study of another formulation of indocyanine green for injection. Below is a description of the FILM Study (NCT 02209532). The study was a randomized, prospective, multi-center, open-label study in patients with early stage uterine or cervical cancer and no known regional nodal or metastatic disease by standard clinical evaluation. Indocyanine green and a blue dye comparator were injected into the cervix of patients at the beginning of the operative procedure. A total of 176 patients were randomized to receive either indocyanine green followed by blue dye or blue dye followed by indocyanine green. A total of four 1 mL injections of a 1.25 mg/ml solution of indocyanine green for a total dose of 5 mg were administered interstitially into the cervix at the 3 o'clock and 9 o'clock positions with a superficial (1 mm to 3 mm) and a deep (1 cm to 3 cm) injection at each position. Lymphatic mapping was performed intraoperatively using a fluorescence imaging device and standard light, followed by excision of tissues identified by indocyanine green, blue dye, or the surgeon's visual and palpation examination. The resected tissues were evaluated by histopathology to confirm presence of lymph nodes. The efficacy of indocyanine green in the detection of lymphatic vessels and lymph nodes during lymphatic mapping procedures was determined by the number of histology-confirmed lymph nodes detected by indocyanine green and/or the blue dye comparator. The mean age of the 176 patients was 63 years (range: 31 to 88 years); distribution by race and ethnicity was 79% White, 4% Black or African American, 3% Asian, 13% Hispanic/Latino and 1% other. Table 1 shows the distribution of resected, confirmed lymph nodes detected by indocyanine green or blue dye in the modified intent-to-treat population (mlTT). Among the confirmed lymph nodes identified, 93% were identified using indocyanine green, and 43% were identified using blue dye, a difference of 50% [95% confidence interval 39% to 60%]. Table 1: Distribution of Resected, Confirmed Lymph Nodes Detected by Indocyanine Green or Blue Dye (BD) Analysis Population Nodes (n) All Lymph Nodes Detected with Indocyanine Green All Lymph Nodes Detected with BD Lymph Nodes Detected with Indocyanine Green Only Lymph Nodes Detected with BD Only Lymph Nodes Detected with Neither mlTT 513 (476/513) (220/513) (262/513) (6/513) (31/513) 93% 43% 51% 1% 6% Table 2 shows the number of patients with at least one resected, confirmed lymph node and the number of patients with at least one bilateral lymph node pair detected by indocyanine green or blue dye. With indocyanine green, approximately 97% of patients had at least one resected, confirmed lymph node detected and 73% had at least one bilateral lymph node pair detected, compared with 68% and 28%, respectively, with blue dye (p-values for each analysis <0.0001). Table 2: Distribution of Patients with at Least One Confirmed Unilateral Lymph Node/ Bilateral Pair Detected by Indocyanine Green or Blue Dye (BD) *: patients with at least one resected confirmed lymph node detected unilaterally **: patients with at least one resected confirmed lymph node detected bilaterally Analysis Population Patients (n) Patients with All Lymph Nodes Detected with Indocyanine Green Patients with All Lymph Nodes Detected with BD Patients with Lymph Nodes Detected with Indocyanine Green only Patients with Lymph Nodes Detected with BD only Patients with Lymph Nodes Detected with Neither mlTT Unilateral* 172 (167/172) 97% (118/172) 68% (51/172) 30% (2/172) 1% (3/172) 3% mlTT Bilateral** (126/172) 73% (49/172) 28% (79/172) 46% (2/172) 1% (44/172) 26%"],"clinical_studies_table":["
Table 1: Distribution of Resected, Confirmed Lymph Nodes Detected by Indocyanine Green or Blue Dye (BD)
Analysis Population
Nodes (n)
All Lymph Nodes Detected with Indocyanine Green
All Lymph Nodes Detected with BD
Lymph Nodes Detected with Indocyanine Green Only
Lymph Nodes Detected with BD Only
Lymph Nodes Detected with Neither
mlTT
513
(476/513)
(220/513)
(262/513)
(6/513)
(31/513)
93%
43%
51%
1%
6%
","
Table 2: Distribution of Patients with at Least One Confirmed Unilateral Lymph Node/ Bilateral Pair Detected by Indocyanine Green or Blue Dye (BD)
*: patients with at least one resected confirmed lymph node detected unilaterally **: patients with at least one resected confirmed lymph node detected bilaterally
Analysis Population
Patients (n)
Patients with All Lymph Nodes Detected with Indocyanine Green
Patients with All Lymph Nodes Detected with BD
Patients with Lymph Nodes Detected with Indocyanine Green only
Patients with Lymph Nodes Detected with BD only
Patients with Lymph Nodes Detected with Neither
mlTT Unilateral*
172
(167/172)97%
(118/172)68%
(51/172)30%
(2/172)1%
(3/172)3%
mlTT Bilateral**
(126/172)73%
(49/172)28%
(79/172)46%
(2/172)1%
(44/172)26%
"],"description":["11 DESCRIPTION Indocyanine Green for injection is an optical imaging agent for intravenous or interstitial use. Each vial contains 25 mg of indocyanine green with not more than 5% sodium iodide as a sterile, lyophilized, green powder. Indocyanine Green has a pH of 5.5-7.5 when reconstituted with Sterile Water for Injection, USP. The chemical name for Indocyanine Green is 1 H Benz[e]indolium, 2-[7-[1,3-dihydro-1,1-dimethyl-3-(4- sulfobutyl)-2 H -benz[e]indol-2-ylidene]-1,3,5-heptatrienyl]-1,1-dimethyl-3-(4-sulfobutyl)-, hydroxide, inner salt, sodium salt. Molecular Formula: C43H47N2NaO6S2; Molecular Mass: 774.96 g/mol, with the following structural formula: Indocyanine green has a peak spectral absorption at 805 nm in blood. Structural Formula"],"effective_time":"20250606","geriatric_use":["8.5 Geriatric Use Of the total number of patients in clinical studies of indocyanine green for visualization of vessels, blood flow and tissue perfusion, 7% were 65 and over, while 1% were 75 and over. Of the total number of patients in clinical studies of indocyanine green for visualization of lymph nodes and lymphatic vessels during lymphatic mapping of cervical and uterine cancer, 9% were 65 and over, while 2% were 75 and over. Clinical studies of indocyanine green for visualization of extrahepatic biliary ducts did not include sufficient numbers of patients aged 65 and over to determine whether they respond differently from younger patients. No overall differences in safety or effectiveness were observed between these patients and younger patients, and other reported clinical experience has not identified differences in responses between elderly and younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal or cardiac function, and of concomitant disease or other drug therapy."],"how_supplied":["16 HOW SUPPLIED/STORAGE AND HANDLING How Supplied Indocyanine Green for injection is supplied as a kit (NDC 70100-424-02) containing the following: Six 25 mL single-patient-use vials of Indocyanine Green (25 mg each) as a sterile, lyophilized green powder for reconstitution NDC 70100-424-01 Six single-dose vials of Sterile Water for Injection (10 mL each) NDC 63323-185-10 or NDC 0409-4887-17 or NDC 0641-6147-01. Storage and Handling Store at 20°C to 25°C (68°F to 77°F)."],"id":"36e9b42b-3b75-09f2-e063-6394a90a12a8","information_for_patients":["17 PATIENT COUNSELING INFORMATION Hypersensitivity Reactions Advise patients to seek medical attention for reactions following injection of Indocyanine Green such as difficulty breathing, swollen tongue or throat, skin reactions including hives, itching and flushed or pale skin, low blood pressure, a weak and rapid pulse and other symptoms or signs of an anaphylactic reaction [see Warnings and Precautions ( 5.1 )] ."],"mechanism_of_action":["12.1 Mechanism of Action When bound to proteins in plasma or in lymph fluid, indocyanine green absorbs light in the near-infrared region with peak absorption at 805 nm and emits fluorescence (light) at a slightly longer wavelength, with peak emission at 830 nm. Fluorescence imaging devices provide external energy as near infrared light for indocyanine green to absorb, resulting in excitation of the indocyanine green, and the emitted light (fluorescence) is transferred from the field of view to an image on a monitor. These optical properties of indocyanine green are utilized in fluorescence imaging of the micro- and macro-vasculature, blood flow and tissue perfusion, the extrahepatic biliary ducts, and for lymphatic mapping of lymph nodes and lymphatic vessels."],"nonclinical_toxicology":["13 NONCLINICAL TOXICOLOGY 13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility No studies have been performed to evaluate the potential for carcinogenicity, mutagenicity, or impairment of fertility by indocyanine green."],"openfda":{},"package_label_principal_display_panel":["PRINCIPAL DISPLAY PANEL - Vial NDC 70100-424-01 Rx only Sterile Indocyanine Green for Injection, USP 25 mg/Vial Single-Patient-Use For Intravenous or Interstitial Use After reconstitution, use within 6 hours. Distributed by: Diagnostic Green LLC 50428 01/2025 Lot No. Exp.: Principal Display Panel - Vial","PRINCIPAL DISPLAY PANEL - STERILE WATER VIAL 10 mL Single-dose Sterile Water for Injection, USP FOR DRUG DILUENT USE Rx only NDC 0409-4887-17 Contains no antimicrobial or other added substance. Sterile, nonpyrogenic. Do not give intravenously unless rendered nearly isotonic. Hospira, Inc. RL-4428 Lake Forest, IL 60045 USA Principal Display Panel - Sterile Water Label","PRINCIPAL DISPLAY PANEL - Carton NDC 70100-424-02 Rx Only - Sterile Indocyanine Green for Injection, USP 25 mg/Vial Single-Patient-Use For Intravenous or Interstitial Use Distributed by: Diagnostic Green LLC Back Panel NDC 70100-424-02 Rx Only - Sterile Recommended Dosage and Reconstitution Instructions: See Prescribing Information Use within 6 hours after reconstitution. STORAGE: Store at 20° to 25° C (68° to 77°F) KIT CONTAINS: • Six vials of Indocyanine Green (25 mg each) • Six Sterile Water for Injection (10 mL each) Indocyanine Green for Injection, USP 25 mg/Vial Single-Patient-Use For Intravenous or Interstitial Use Left Panel Indocyanine Green for Injection, USP Distributed by: Diagnostic Green LLC Farmington Hills MI 48331 USA Manufactured by: Patheon Italia S.p.A. 20052 Monza (Milano) ITALY or Lyocontract GmbH 38871 Ilsenburg GERMANY Sterile Water Manufactured by: Hospira, Inc. Rocky Mount, NC 27804 or Fresenius Kabi USA, LLC Grand Island, NY 14072 or Hikma Pharmaceuticals Berkeley Heights, NJ 07922 01/2025 Principal Display Panel - Carton"],"pediatric_use":["8.4 Pediatric Use Use of Indocyanine Green for visualization of vessels, blood flow and tissue perfusion has been established in pediatric patients aged 1 month and older. Pediatric use is supported by published data in 49 pediatric patients who received indocyanine green for assessment of blood flow and tissue perfusion in cardiovascular, vascular, and plastic, micro- and reconstructive surgical procedures, and by clinical trials in adults . No overall differences in safety or effectiveness have been observed between pediatric patients and adults. The dose range was similar to the effective dose range in adults [see Dosage and Administration ( 2.1 )]. The use of Indocyanine Green for visualization of vessels, blood flow and tissue perfusion has not been established in pediatric patients aged less than 1 month. Use of Indocyanine Green for visualization of extrahepatic biliary ducts has been established in pediatric patients aged 12 years and older. Pediatric use is supported by clinical trials in adults in addition to clinical use in pediatric patients. No overall differences in safety or effectiveness have been observed between pediatric patients and adults. The dose range was similar to the effective dose range in adults [see Dosage and Administration ( 2.2 )] . The use of Indocyanine Green for visualization of extrahepatic biliary ducts has not been established in pediatric patients aged less than 12 years. Use of Indocyanine Green for visualization of lymph nodes and lymphatic vessels during lymphatic mapping for cervical and uterine cancer have not been established in pediatric patients. Use of Indocyanine Green for ophthalmic angiography has been established in pediatric patients. Pediatric use is supported by evidence from the published literature."],"pharmacodynamics":["12.2 Pharmacodynamics There are no pharmacodynamic data."],"pharmacokinetics":["12.3 Pharmacokinetics Distribution Following intravenous injection, indocyanine green binds to plasma proteins (98%) and is largely confined to the intravascular compartment. Indocyanine green undergoes no significant extrahepatic or enterohepatic circulation; simultaneous arterial and venous blood estimations have shown negligible renal, peripheral, lung or cerebro-spinal uptake of the dye. After biliary obstruction, the dye appears in the hepatic lymph, independently of the bile, suggesting that the biliary mucosa is sufficiently intact to prevent diffusion of the dye, though allowing diffusion of bilirubin. Following interstitial injection, indocyanine green binds to proteins in lymph fluid and the interstitial space, is taken up by the lymphatic vessels, and drains to the lymph nodes. Since excessive dye extravasation does not take place in the highly fenestrated choroidal vasculature, Indocyanine Green is useful in both absorption and fluorescence infrared angiography of the choroidal vasculature when using appropriate filters and film in a fundus camera. Elimination Indocyanine green is taken up from the plasma almost exclusively by the hepatic parenchymal cells and is secreted entirely into the bile."],"pregnancy":["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."],"risks":["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.","Risk Summary Seventeen cases of indocyanine green use in lactating women have been reported in the scientific literature with no adverse events observed in the breastfed infant. However, there are no data on the presence of indocyanine green in human milk or the effects on milk production. Therefore, the developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for Indocyanine Green and any potential adverse effects on the breastfed infant from Indocyanine Green or from the underlying maternal condition."],"set_id":"36e9a978-db63-01b6-e063-6394a90a4d66","spl_product_data_elements":["Indocyanine Green Indocyanine Green and Water Indocyanine Green Indocyanine Green INDOCYANINE GREEN INDOCYANINE GREEN ACID FORM Sterile Water Water WATER WATER"],"spl_unclassified_section":["Manufactured by: Patheon Italia S.p.A. 20900 Monza (MB), ITALY or LYOCONTRACT GmbH 38871 Ilsenburg, GERMANY Distributed by: Diagnostic Green LLC Farmington Hills, Ml 48331 Sterile Water for injection, USP is manufactured by: Fresenius Kabi USA, LLC Grand Island, NY 14072 or Hospira, Inc. Rocky Mount, NC 27804 or Hikma Pharmaceuticals USA Inc. Cherry Hill, NJ 08003 50426"],"use_in_specific_populations":["8 USE IN SPECIFIC POPULATIONS 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. 8.2 Lactation Risk Summary Seventeen cases of indocyanine green use in lactating women have been reported in the scientific literature with no adverse events observed in the breastfed infant. However, there are no data on the presence of indocyanine green in human milk or the effects on milk production. Therefore, the developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for Indocyanine Green and any potential adverse effects on the breastfed infant from Indocyanine Green or from the underlying maternal condition. 8.4 Pediatric Use Use of Indocyanine Green for visualization of vessels, blood flow and tissue perfusion has been established in pediatric patients aged 1 month and older. Pediatric use is supported by published data in 49 pediatric patients who received indocyanine green for assessment of blood flow and tissue perfusion in cardiovascular, vascular, and plastic, micro- and reconstructive surgical procedures, and by clinical trials in adults . No overall differences in safety or effectiveness have been observed between pediatric patients and adults. The dose range was similar to the effective dose range in adults [see Dosage and Administration ( 2.1 )]. The use of Indocyanine Green for visualization of vessels, blood flow and tissue perfusion has not been established in pediatric patients aged less than 1 month. Use of Indocyanine Green for visualization of extrahepatic biliary ducts has been established in pediatric patients aged 12 years and older. Pediatric use is supported by clinical trials in adults in addition to clinical use in pediatric patients. No overall differences in safety or effectiveness have been observed between pediatric patients and adults. The dose range was similar to the effective dose range in adults [see Dosage and Administration ( 2.2 )] . The use of Indocyanine Green for visualization of extrahepatic biliary ducts has not been established in pediatric patients aged less than 12 years. Use of Indocyanine Green for visualization of lymph nodes and lymphatic vessels during lymphatic mapping for cervical and uterine cancer have not been established in pediatric patients. Use of Indocyanine Green for ophthalmic angiography has been established in pediatric patients. Pediatric use is supported by evidence from the published literature. 8.5 Geriatric Use Of the total number of patients in clinical studies of indocyanine green for visualization of vessels, blood flow and tissue perfusion, 7% were 65 and over, while 1% were 75 and over. Of the total number of patients in clinical studies of indocyanine green for visualization of lymph nodes and lymphatic vessels during lymphatic mapping of cervical and uterine cancer, 9% were 65 and over, while 2% were 75 and over. Clinical studies of indocyanine green for visualization of extrahepatic biliary ducts did not include sufficient numbers of patients aged 65 and over to determine whether they respond differently from younger patients. No overall differences in safety or effectiveness were observed between these patients and younger patients, and other reported clinical experience has not identified differences in responses between elderly and younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal or cardiac function, and of concomitant disease or other drug therapy."],"version":"10"}