NDC 66259-903 Spy-phi Kit

Indocyanine Green

NDC Product Code 66259-903

NDC 66259-903-14

Package Description: 1 KIT in 1 KIT * 1 INJECTION, POWDER, LYOPHILIZED, FOR SOLUTION in 1 VIAL (66259-146-01) * 10 mL in 1 VIAL, PLASTIC

NDC 66259-903-24

Package Description: 6 KIT in 1 CASE > 1 KIT in 1 KIT * 1 INJECTION, POWDER, LYOPHILIZED, FOR SOLUTION in 1 VIAL (66259-146-01) * 10 mL in 1 VIAL, PLASTIC

NDC Product Information

Spy-phi Kit with NDC 66259-903 is a a human prescription drug product labeled by Novadaq Technologies Inc. The generic name of Spy-phi Kit is indocyanine green. The product's dosage form is kit and is administered via intravascular; intravenous form.

Labeler Name: Novadaq Technologies Inc

Dosage Form: Kit - A packaged collection of related material.

Product Type: Human Prescription Drug What kind of product is this?
Indicates the type of product, such as Human Prescription Drug or Human Over the Counter Drug. This data element matches the “Document Type” field of the Structured Product Listing.

Administration Route(s)

What are the Administration Route(s)?
The translation of the route code submitted by the firm, indicating route of administration.

  • Intravascular - Administration within a vessel or vessels.
  • Intravenous - Administration within or into a vein or veins.

Product Labeler Information

What is the Labeler Name?
Name of Company corresponding to the labeler code segment of the Product NDC.

Labeler Name: Novadaq Technologies Inc
Labeler Code: 66259
FDA Application Number: NDA211580 What is the FDA Application Number?
This corresponds to the NDA, ANDA, or BLA number reported by the labeler for products which have the corresponding Marketing Category designated. If the designated Marketing Category is OTC Monograph Final or OTC Monograph Not Final, then the Application number will be the CFR citation corresponding to the appropriate Monograph (e.g. “part 341”). For unapproved drugs, this field will be null.

Marketing Category: NDA - A product marketed under an approved New Drug Application. What is the Marketing Category?
Product types are broken down into several potential Marketing Categories, such as NDA/ANDA/BLA, OTC Monograph, or Unapproved Drug. One and only one Marketing Category may be chosen for a product, not all marketing categories are available to all product types. Currently, only final marketed product categories are included. The complete list of codes and translations can be found at www.fda.gov/edrls under Structured Product Labeling Resources.

Start Marketing Date: 09-10-2019 What is the Start Marketing Date?
This is the date that the labeler indicates was the start of its marketing of the drug product.

Listing Expiration Date: 12-31-2020 What is the Listing Expiration Date?
This is the date when the listing record will expire if not updated or certified by the product labeler.

Exclude Flag: N What is the NDC Exclude Flag?
This field indicates whether the product has been removed/excluded from the NDC Directory for failure to respond to FDA’s requests for correction to deficient or non-compliant submissions. Values = ‘Y’ or ‘N’.

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Spy-phi Kit Product Labeling Information

The product labeling information includes all published material associated to a drug. Product labeling documents include information like generic names, active ingredients, ingredient strength dosage, routes of administration, appearance, usage, warnings, inactive ingredients, etc.

Product Labeling Index

1.1 Visualization Of Vessels, Blood Flow And Tissue Perfusion

  • SPY AGENT™ GREEN is indicated in adults and pediatric patients one month of age and older for:fluorescence imaging of micro- and macro-vasculature, blood flow and tissue perfusion before, during and after vascular, gastrointestinal, organ transplant, and plastic, micro- and reconstructive surgeries, including general minimally invasive surgical procedures.

1.2 Visualization Of Extrahepatic Biliary Ducts

  • SPY AGENT™ GREEN is indicated in adults and pediatric patients aged 12 to 17 years for:fluorescence imaging of extrahepatic biliary ducts.

1.3 Visualization Of Lymph Nodes And Lymphatic Vessels During Lymphatic Mapping For Cervical And Uterine Tumors

  • SPY AGENT™ GREEN is indicated in women for:fluorescence imaging of lymph nodes and delineation of lymphatic vessels in the cervix and uterus during lymphatic mapping in patients with solid tumors for which this procedure is a component of intraoperative management.

DosingAdults: The recommended dose of SPY AGENT GREEN for a single image
sequence is 1.25 mg to 5 mg of a 2.5 mg/mL solution.For visualization of perfusion in extremities through the skin, the recommended dose is 3.75 mg to 10 mg of a 2.5 mg/mL solution. Immediately flush with a 10 mL bolus of 0.9% Sodium Chloride, USP.Pediatric patients:The recommended dose for a single image sequence is 1.25 mg to 5 mg
SPY AGENT GREEN 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.Additional doses may be administered to obtain imaging sequences during the procedure. Do not exceed the maximum total dose of 2 mg/kg.AdministrationPrior to the imaging procedure, draw up the desired dosage of SPY AGENT GREEN solution into
appropriate syringes and prepare a 10 mL syringe of 0.9% Sodium Chloride, 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 for Visualization of Vessels, Blood Flow and Tissue PerfusionSPY AGENT GREEN may be used with either the SPY® Elite or PINPOINT® Fluorescence Imaging Systems or with a FDA
cleared or approved imaging device that is specifically intended for fluorescence imaging with indocyanine green.A fluorescence response should be visible in blood vessels within 5 to 15 seconds after injection.

Dosing and AdministrationThe recommended single dose of SPY AGENT GREEN for adults and
pediatric patients aged 12 to 17 years is 2.5 mg of a 2.5 mg/mL solution administered intravenously as a single dose 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 for Visualization of Extrahepatic Biliary Ducts
SPY AGENT GREEN may be used with the PINPOINT® Fluorescence Imaging System or with a FDA cleared or approved imaging device that
is specifically intended for fluorescence imaging with indocyanine green. Fluorescence is visible in the biliary tree within 45 minutes after injection.

Dosing and AdministrationThe recommended single dose of SPY AGENT GREEN is
5 mg of a 1.25 mg/mL solution (four 1 mL injections administered interstitially into the cervix, at the three o’ clock and the
nine o’clock positions with a superficial (1 mm to 3 mm) and a deep (1 cm to 2 cm) injection at each position).Imaging Instructions for Visualization of Lymph Nodes and Lymphatic Vessels During Lymphatic MappingSPY AGENT GREEN may be used with the PINPOINT® Fluorescence Imaging System or with a FDA cleared or approved imaging
device that is specifically intended for fluorescence imaging with indocyanine green.Fluorescent lymphatic vessels and lymph nodes should begin to be visible within 1 minute after injection.

2.4 Reconstitution Instructions

  • GeneralPrepare 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, and Tissue Perfusion and Visualization of Extrahepatic Biliary DuctsDissolve SPY AGENT GREEN with 10 mL Sterile Water for Injection, USP to form a concentration of 2.5 mg indocyanine green/mL.Visualization of Lymph Nodes and Lymphatic Vessels During Lymphatic MappingDissolve SPY AGENT GREEN with 20 mL Sterile Water for Injection, USP to form a concentration of 1.25 mg indocyanine green/mL.

3 Dosage Forms And Strengths

SPY AGENT GREEN (indocyanine green for injection, USP) is a sterile lyophilized green powder containing 25 mg of indocyanine green
with no more than 5% sodium iodide provided in a 20 mL single-patient use vial.

4 Contraindications

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)].

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)]. Always have cardiopulmonary resuscitation personnel and
equipment readily available and monitor all patients for hypersensitivity reactions.

5.2 Interference With 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 a week following administration of
SPY AGENT GREEN [see Drug Interactions (7)].

6 Adverse Reactions

  • The following adverse reactions are discussed in greater detail in other sections of the label: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.

7 Drug Interactions

Effect on Radioactive Iodine UptakeBecause 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
[see Warnings and Precautions (5.2)].

8.1 Pregnancy

Risk SummaryThere are no adequate and well-controlled studies of SPY AGENT
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 SummarySeventeen 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 SPY AGENT GREEN and any potential adverse effects on the breastfed infant from SPY AGENT 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 one 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 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 less than
one month of age.Use of indocyanine green for visualization of extrahepatic biliary ducts has been established in pediatric patients aged
12 to 17 years. 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 less 12 years of age.The safety and efficacy of indocyanine green for visualization of lymph nodes and lymphatic vessels during lymphatic
mapping for cervical and uterine tumors has not been established in pediatric patients.

8.5 Geriatric Use

Of the total number of subjects in clinical studies of SPY AGENT GREEN in visualization of vessels, blood flow, and tissue
perfusion, 7 percent were 65 and over, while 1 percent were 75 and over and of the total number of subjects in clinical studies
of SPY AGENT GREEN in visualization of lymph nodes and lymphatic vessels during lymphatic mapping, 9 percent were 65 and over, while
2 percent were 75 and over. No overall differences in safety or effectiveness were observed between these subjects and younger subjects, and
other reported clinical experience has not identified differences in responses between the elderly and younger patients, but greater sensitivity
of some older individuals cannot be ruled out.Clinical studies of SPY AGENT GREEN in visualization of extrahepatic biliary ducts did not include sufficient numbers of
subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience
has not identified differences in responses between the 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.

11 Description

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 or interstitial use. Each vial contains a sterile, lyophilized green powder
containing 25 mg of indocyanine green with not more than 5% sodium iodide. 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: C43H47N2NaO6S2; Molecular Mass: 774.96 g/mol, with the following structural formula:Indocyanine green has a peak spectral absorption at 800 nm. SPY AGENT GREEN has a pH of 5.5 to 7.5 when reconstituted with
Sterile Water for Injection, USP.

12.1 Mechanism Of Action

When bound to proteins in plasma or in lymph fluid, indocyanine green absorbs light in the near-infrared region at 806 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 ICG to absorb, resulting in excitation of the ICG 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 is no relevant pharmacodynamic data.

12.3 Pharmacokinetics

DistributionFollowing 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 is taken up by the lymphatic vessels and lymph nodes.EliminationIndocyanine green is taken up from the plasma almost exclusively by
the hepatic parenchymal cells and is secreted entirely into the bile.The plasma fractional disappearance rate at a 0.5 mg/kg dose has been reported to be significantly greater in women than
in men, although there was no significant difference in the calculated value for clearance.

14 Clinical Studies

Visualization of Lymph Nodes and Lymphatic Vessels During Lymphatic Mapping of Cervical and
Uterine TumorsFILM Study (NCT 02209532)FILM was a randomized, prospective, multi-center,
open-label study in patients with early stage uterine or cervical cancers and no known regional nodal or metastatic disease by standard
clinical evaluation. SPY AGENT 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 SPY AGENT GREEN followed by blue dye or blue dye
followed by SPY AGENT GREEN. A total of four 1 ml injections of a 1.25 mg/ml solution of SPY AGENT GREEN were administered into the
cervix at the 3 and 9 o’clock positions with a superficial (1 to 3 mm) and a deep (1 to 3 cm) injection at each position for a total
dose of 5 mg per patient. Lymphatic mapping was performed intraoperatively using the PINPOINT® Fluorescence Imaging System and standard
light, followed by excision of tissues identified by SPY AGENT 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 SPY AGENT GREEN and the
PINPOINT® Fluorescence Imaging System 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 SPY AGENT GREEN and/or the blue dye comparator.Table 1 shows the distribution of resected, confirmed lymph nodes by the presence or absence of SPY AGENT GREEN or blue dye in the
modified intent-to-treat population (mITT). Among the confirmed lymph nodes identified, 93% were identified using SPY AGENT 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 SPY AGENT GREEN or Blue Dye (BD)Analysis populationNodes (n)All Lymph Nodes Detected with SPY AGENT GREENAll Lymph Nodes Detected with BD Lymph Nodes Detected with SPY AGENT GREEN OnlyLymph Nodes Detected with BD OnlyLymph Nodes Detected with NeithermITT513(476/513)93%(220/513)43%(262/513)51%(6/513)1%(31/513)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 SPY AGENT GREEN or blue dye. With SPY AGENT 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 SPY AGENT 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 bilaterallyAnalysis populationPatients (n) Patients with All Lymph Nodes Detected with SPY AGENT GREENPatients withAll Lymph Nodes Detected with BD Patients withLymph Nodes Detected with SPY AGENT GREEN OnlyPatients withLymph Nodes Detected with BD OnlyPatients withLymph Nodes Detected with NeithermITTUnilateral*172(167/172)97%(118/172)68%(51/172)30%(2/172)1%(3/172)3%mITT Bilateral**(126/172)73%(49/172)28%(79/172)46%(2/172)1%(44/172)26%

16 How Supplied/Storage And Handling

NDC 66259-146-01SPY AGENT GREEN (indocyanine green for injection, USP) is supplied as 25 mg of lyophilized powder in a 20 mL single patient use vial in the following configurations:            ComponentsSpy Elite KitNDC 66259-306-13Kit for use with SPY Elite System
For visualization of vessels, blood flow, and tissue perfusion
One 25 mg SPY AGENT GREEN (Indocyanine Green for Injection, USP) vial,One 10 mL Sterile Water for Injection, USP plastic vial,One ND8000 sterile drapeSpy Elite PackNDC 66259-306-236 SPY Elite kits:
Six 25 mg SPY AGENT GREEN (Indocyanine Green for Injection, USP) vials,
Six 10 mL Sterile Water for Injection, USP plastic vials,
Six ND8000 sterile drapes
PINPOINT KitNDC 66259-036-11Kit for use with PINPOINT System
For visualization of vessels, blood flow, and tissue perfusion
For visualization of extrahepatic biliary ducts
One 25 mg SPY AGENT GREEN (Indocyanine Green for Injection, USP) vial,
One 10 mL Sterile Water for Injection, USP plastic vial,
Two 3 ml syringes (sterile),
Two 10 ml syringes (sterile),
One 3-way stopcock (sterile),
Two 18G, 1 inch needles (sterile),
Labels for syringes
PINPOINT PackNDC 66259-036-216 PINPOINT kits:
Six 25 mg SPY AGENT GREEN (Indocyanine Green for Injection, USP) vials,
Six 10 mL Sterile Water for Injection, USP plastic vials,
Twelve 3 ml syringes (sterile),
Twelve 10 ml syringes (sterile),
Six 3-way stopcocks (sterile),
Twelve 18G, 1 inch needles (sterile),
Labels for syringes
PINPOINT Lymphatics KitNDC 66259-037-12Kit for use with PINPOINT System
For lymphatic mapping
One 25 mg SPY AGENT GREEN (Indocyanine Green for Injection, USP) vial,
Two 10 mL Sterile Water for Injection, USP plastic vials,
One 10 ml syringe (sterile),
One luer-lock 10 ml syringe with controlled handle (sterile), Two spinal needles 22G, 3.5 inch (sterile),
Labels for syringes
PINPOINT Lymphatics PackNDC 66259-037-226 PINPOINT lymphatics kits
Six 25 mg SPY AGENT GREEN (Indocyanine Green for Injection, USP) vials,
Twelve 10 mL Sterile Water for Injection, USP plastic vials,
Six 10 ml syringes (sterile),
Six luer-lock 10 ml syringes with controlled handle (sterile), Twelve spinal needles 22G, 3.5 inch (sterile)
Labels for syringes
NDC 63323-185-10 (or NDC 0409-4887-10) Sterile Water for Injection, USP, 10 mL fill in 10 mL plastic vials.STORAGE: Store at 20°C to 25°C (68°F to 77°F) [See USP Controlled Room Temperature]. PATIENT COUNSELING INFORMATIONHypersensitivity ReactionsAdvise patients to seek medical attention for reactions following injection of SPY AGENT 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)].Manufactured by:
Patheon Italia S.p.A.
Ferentino (FR), Italy
Distributed by:
Novadaq Technologies ULC
8329 Eastlake Drive, Unit 101,
Burnaby, BC, Canada V5A 4W2
Sterile Water for Injection, USP is manufactured by:
Fresenius Kabi USA, LLC
Grand Island, NY 14072 U.S.A.or
Hospira, Inc.
Rocky Mount, NC 27804 U.S.A.

* Please review the disclaimer below.