Drug Safety-related Labeling Changes (SrLC)

Get Email Alerts | Guide

Drug Safety-related Labeling Changes (SrLC) Database

ANDA	Abbreviated New Drug Application
BLA	Biologics License Application
CDER	Center for Drug Evaluation and Research
MG	Medication Guide
NDA	New Drug Application
PCI	Patient Counseling Information
PI	Patient Information
PLR	Physician Labeling Rule
PLLR	Pregnancy and Lactation Labeling Rule
Italics	For the most part, italics indicate an FDA comment such as: Additions and/or revisions underlined These italics usually appear at the beginning of the section. In some cases, italics may be an inherent part of the label, and will most often appear in the body of the section.
Underlines	Any text that is underlined indicates text that has been added or revised. There are exceptions where underlining occurs in a section subtitle or heading. This is the case when there is just one word underlined in the body of the text.

Sections

BW	Box Warning
WP	Warnings and Precautions all in one section (PLR-format) Warnings as one section (pre-PLR format) Precautions as one section (pre-PLR format)
AR	Adverse Reactions (in pre-PLR format, this may be a subheading under precautions).
DI	Drug Interactions (in pre-PLR format, this may be a subheading under precautions).
USP	Use in Specific Populations (Inclusive on one or more of the following: Pregnancy; Lactation (PLLR- format); Nursing Mothers (pre-PLLR format); Females and Males of Reproductive Potential (PLLR format only); Pediatric Use, Geriatric Use, Renal Impairment, Hepatic Impairment, Sex, Race (these last six may be a subheading of precautions if label in pre-PLLR format.
PCI/PI/MG	Patient Counseling Information (PLR format only) - summarizes the information that a health care provider should convey to a patient (or caregiver when applicable) when a counseling discussion is taking place (e.g., a physician prescribing a drug during an office visit, a nurse providing discharge instructions at a hospital, or a pharmacist conveying information at a pharmacy). Patient Information - FDA approved patient labeling. Medication Guide - paper handouts that come with many prescription medicines. The guides address issues that are specific to particular drugs and drug classes, and they contain FDA-approved information that can help patients avoid serious adverse events.

Only NDAs and CDER regulated BLAs are included in this database. ANDAs are not included.

Applications that remain active, even if the product has been discontinued, undergo safety-related labeling changes.

SPY AGENT GREEN KIT (NDA-211580)

(INDOCYANINE GREEN)

Safety-related Labeling Changes Approved by FDA Center for Drug Evaluation and Research (CDER)

Download Data

Expand all

06/05/2023 (SUPPL-6)

Approved Drug Label (PDF)

5 Warnings and Precautions

5.1 Hypersensitivity Reactions

Additions and/or revisions underlined:

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

Subsection title revised

6 Adverse Reactions

Additions and/or revisions underlined:

The following clinically significant adverse reactions are described elsewhere in the labeling:

Hypersensitivity Reactions [see Warnings and Precautions (5.1)].

6.1 Clinical Trials Experience

Newly added subsection:

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

Additions and/or revisions underlined:
Newly added subsection:

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.

7 Drug Interactions

Additions and/or revisions underlined:

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.

8 Use in Specific Populations

8.4 Pediatric Use

Additions and/or revisions underlined:

Use of SPY AGENT 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, 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 SPY AGENT GREEN for visualization of vessels, blood flow and tissue perfusion has not been established in pediatric patients aged less than 1 month.Use of SPY AGENT 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 SPY AGENT GREEN for visualization of extrahepatic biliary ducts has not been established in pediatric patients aged less than 12 years.

The safety and efficacy of SPY AGENT GREEN for visualization of lymph nodes and lymphatic vessels during lymphatic mapping for cervical and uterine cancer and breast cancer have not been established in pediatric patients.

8.5 Geriatric Use

Additions and/or revisions underlined:

Of the total number of patients in clinical studies of SPY AGENT GREEN in 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 SPY AGENT GREEN in 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. Of the total number of patients in clinical studies of SPY AGENT GREEN in visualization of lymph nodes and lymphatic vessels during lymphatic mapping of breast cancer, 38% were 65 and over, while 8% were 75 and over.

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.

Clinical studies of SPY AGENT GREEN in 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. 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.