İHALE DÜNYASI
İHALE DÜNYASI
SPY AGENT GREEN (indocyanine green for injection, USP) is a water soluble, optical imaging agent which is reconstituted with Sterile Water for Injection, USP, for intravenous, interstitial or intradermal use. Each vial contains a sterile, lyophilized, green powder containing 25 mg of indocyanine green with not more than 5% sodium iodide. Hydrochloric acid or sodium hydroxide may be used to adjust the pH prior to lyophilization. The chemical name for Indocyanine Green is 1 HBenz[e]indolium, 2-[7-[1,3-dihydro-1,1-dimethyl-3-(4-sulfobutyl)-2H-benz[e] indol-2-ylidene]-1,3,5-heptatrienyl]-1,1-dimethyl-3-(4-sulfobutyl)-, hydroxide, inner salt, sodium salt. Molecular Formula: C 43 H 47 N 2 NaO 6 S 2 ; Molecular Mass: 774.96 g/mol, with the following structural formula: Indocyanine green has a peak spectral absorption at 805 nm. SPY AGENT GREEN has a pH of 5.5 to 7.5 when reconstituted with Sterile Water for Injection, USP. Chemical Structure
SPY AGENT GREEN is an optical imaging agent indicated for use with a fluorescence imaging device for: Visualization 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 one month of age and older. ( 1.1 ) Visualization of extrahepatic biliary ducts in adults and pediatric patients aged 12 years and older. ( 1.2 ) Visualization of lymph nodes and lymphatic vessels during lymphatic mapping in adults with cervical and uterine cancer. ( 1.3 ) Visualization of lymph nodes and lymphatic vessels during lymphatic mapping in adults with breast cancer. ( 1.4 ) 1.1 Visualization of Vessels, Blood Flow and Tissue Perfusion SPY AGENT 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 SPY AGENT 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 SPY AGENT 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 Lymphatic Mapping of Breast Cancer SPY AGENT GREEN is indicated for fluorescence imaging of lymph nodes and delineation of lymphatic vessels during lymphatic mapping in adults with breast cancer for which this procedure is a component of intraoperative management.
Visualization of vessels, blood flow and tissue perfusion (2.5 mg/mL solution) 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. 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. 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) 2.5 mg by intravenous injection at least 45 minutes prior to surgery. 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) 5 mg interstitially as four 1 mL injections. See Full Prescribing Information for injection techniques. ( 2.3 ) Lymphatic mapping of breast cancers in adults (2.5 mg/mL solution) 0.25 mg per breast intradermally as two 0.05 mL peri-areolar injections. A subsequent peri-tumoral dose of 0.375 mg per breast (three 0.05 mL injections) may be administered intradermally. See Full Prescribing Information for injection techniques. ( 2.4 ) See Full Prescribing Information for reconstitution instructions. ( 2.5 ). 2.1 Recommended Dose, Administration and Imaging for Visualization of Vessels, Blood Flow and Tissue Perfusion Dosing Adults: The recommended dose of SPY AGENT 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, USP. Pediatric patients aged 1 month and older: The recommended dose of SPY AGENT 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 SPY AGENT GREEN solution into appropriate syringes and prepare a 10 mL syringe of 0.9% Sodium Chloride Injection, USP. 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 SPY AGENT GREEN into the line as a tight bolus. Immediately switch the access on the stopcock and inject the prepared flush. Imaging Instructions SPY AGENT GREEN may be used with either the SPY(R) Elite or PINPOINT(R) Fluorescence Imaging Systems or with a FDA cleared or approved imaging device that is specifically indicated for use 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 SPY AGENT 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 SPY AGENT GREEN may be used with the PINPOINT (R) Fluorescence Imaging System or with a FDA cleared or approved imaging device that is specifically indicated for use 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 SPY AGENT 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 SPY AGENT GREEN may be used with the PINPOINT (R) Fluorescence Imaging System or with a FDA cleared or approved imaging device that is specifically indicated for use 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, Administration and Imaging for Lymphatic Mapping of Breast Cancer Dosing and Administration The recommended dose of SPY AGENT GREEN for lymphatic mapping of breast cancer in adults is 0.25 mg per breast administered intradermally as two 0.05 mL injections of a 2.5 mg/mL solution into the peri-areolar area at the 12 o'clock and the 9 o'clock positions for the right breast or at the 12 o'clock and 3 o'clock positions for the left breast. If lymphatic flow towards the axillary lymph nodes is not visualized, a subsequent peri-tumoral dose of 0.375 mg (three 0.05 mL injections intradermally at the 12 o'clock, 3 o'clock and 9 o'clock positions) is recommended. Imaging Instructions SPY AGENT GREEN may be used during open field surgery with the SPY Portable Handheld Imaging (SPY-PHI (R) ) System or with a FDA cleared or approved imaging device that is specifically indicated for use with indocyanine green for fluorescence imaging of lymph nodes and delineation of lymphatic vessels during lymphatic mapping of breast cancer. Fluorescent lymphatic vessels and lymph nodes should begin to be visible within 1 minute after injection. 2.5 Reconstitution Instructions General Prepare SPY AGENT GREEN under sterile conditions prior to surgery. 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 and Lymphatic Mapping of Breast Cancer Dissolve SPY AGENT GREEN with 10 mL Sterile Water for Injection, USP to form a concentration of 2.5 mg indocyanine green/mL. Lymphatic Mapping of Cervical and Uterine Cancer Dissolve SPY AGENT GREEN with 20 mL Sterile Water for Injection, USP to form a concentration of 1.25 mg indocyanine green/mL.
SPY AGENT 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 )
The following adverse reactions are discussed in greater detail in other sections of the label: Hypersensitivity Reactions [see Warnings and Precautions ( 5.1 )] . Lymphatic mapping of breast cancers: Most common adverse reactions were skin and injection site discoloration in two patients (1.4%). ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Stryker Corp. at 1-800-624-4422 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch . 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. Lymphatic Mapping of Breast Cancer In an open-label, single arm, clinical trial, 151 patients with breast cancer received a single dose of 0.25 mg SPY AGENT GREEN intradermally into the peri-areolar area. Five patients received a subsequent peri-tumoral injection of 0.375 mg intradermally in addition to the peri-areolar dose of 0.25 mg [see Clinical Studies ( 14.2 )]. Skin discoloration including injection site discoloration were reported in two patients (1.4%). 6.2 Postmarketing Experience The following adverse reactions have been identified during post-approval use of indocyanine green products including SPY AGENT 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.
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 ( 6.2 )] . SPY AGENT 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 SPY AGENT GREEN contains iodine, the iodine-binding capacity of thyroid tissue may be reduced for at least one week following administration [see Drug Interactions ( 7 )] .
Interference with Thyroid Radioactive Iodine Uptake Studies Because SPY AGENT GREEN contains iodine, 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 SPY AGENT GREEN. Interference with Thyroid Radioactive Iodine Uptake Studies: Do not perform radioactive iodine uptake studies for at least a week following the use of SPY AGENT GREEN. ( 7 )