Drug Safety-related Labeling Changes (SrLC)

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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.

CARDIOGEN-82 (NDA-019414)

(RUBIDIUM CHLORIDE RB-82)

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

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12/23/2024 (SUPPL-34)

Approved Drug Label (PDF)

5 Warnings and Precautions

5.1 High Level Radiation Exposure with Use of Incorrect Eluent

Additions and/or revisions underlined:

Additives present in solutions (particularly calcium ions) used by mistake to elute CardioGen-82 expose patients to high levels of radiation by causing the release of large amounts of Sr 82 and Sr 85 into the eluate regardless of the generator’s age or prior use. When solutions containing calcium ions are used, high levels of radioactivity are present in any subsequent eluate even with the use of additive-free 0.9% Sodium Chloride Injection.

Use only additive-free 0.9% Sodium Chloride Injection to elute CardioGen-82. If an incorrect eluent is used, immediately stop the patient infusion, evaluate the patient’s radiation absorbed dose, and monitor for the effects of radiation to critical organs such as bone marrow. Permanently discontinue use of the affected CardioGen-82 generator [see Dosage and Administration (2.5)].

6 Adverse Reactions

Addition of the following to the bulleted line listing:

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

High Level Radiation Exposure with Use of Incorrect Eluent [see Warnings and Precautions (5.1)]
Excess Radiation Exposure with Failure to Follow Eluate Testing Protocol [see Warnings and Precautions (5.2)]

10/15/2020 (SUPPL-21)

Approved Drug Label (PDF)

17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)

PATIENT COUNSELING INFORMATION

Additions and/or revisions underlined:

Pregnancy

Advise a pregnant woman of the potential risk to a fetus [see Use in Specific Populations (8.1)].

Lactation

Advise lactating women that exposure to Rb-82 chloride through breast milk can be minimized if breastfeeding is discontinued when Rb 82 chloride injection is administered. Advise lactating women not to resume breastfeeding for at least one hour after completion of rubidium Rb 82 infusion [see Use in Specific Populations (8.2)].

Post-Study Voiding

Instruct patients to void after completion of each image acquisition session and as often as possible for one hour after completion of the PET scan [see Warnings and Precautions (5.5)].

10/24/2019 (SUPPL-24)

Approved Drug Label (PDF)

8 Use in Specific Populations

8.1 Pregnancy

(Pregnancy and Lactation Labeling Rule (PLLR) conversion)

Risk Summary

There are no data available on the use of rubidium Rb 82 chloride in pregnant women. Animal reproductive studies have not been conducted with rubidium Rb 82 chloride injection. However, all radiopharmaceuticals have the potential to cause fetal harm depending on the fetal stage of development and the magnitude of the radiation dose. If considering rubidium Rb 82 chloride injection administration to a pregnant woman, inform the patient about the potential for adverse pregnancy outcomes based on the radiation dose from rubidium Rb 82 and the gestational timing of exposure.

The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively.

8.2 Lactation

(Pregnancy and Lactation Labeling Rule (PLLR) conversion)

Risk Summary

There is no information regarding the presence of Rb 82 chloride in human milk, the effects on the breastfed infant or the effects on milk production. Due to the short half-life of rubidium Rb 82 (75 seconds), exposure of a breastfed infant through breast milk can be minimized by temporary discontinuation of breastfeeding [See Clinical Considerations]. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for rubidium Rb 82 chloride injection, any potential adverse effects on the breastfed child from Rb 82 or from the underlying maternal condition.

Clinical Considerations

Minimizing Exposure

Exposure to Rb 82 chloride through breast milk can be minimized if breastfeeding is discontinued when Rb 82 chloride injection is administered. Do not resume breastfeeding until at least one hour after completion of rubidium Rb 82 chloride injection infusion.

04/26/2019 (SUPPL-22)

Approved Drug Label (PDF)

Boxed Warning

Revised; Full text below:

WARNING: HIGH LEVEL RADIATION EXPOSURE WITH USE OF INCORRECT ELUENT AND FAILURE TO FOLLOW THE ELUATE TESTING PROTOCOL

High Level Radiation Exposure with Use of Incorrect Eluent

Patients are exposed to high radiation levels when the CardioGen-82 generator is eluted with the incorrect eluent due to high Sr 82 and Sr 85 breakthrough levels

Use only additive-free 0.9% Sodium Chloride Injection USP to elute the generator.
Immediately stop the patient infusion and permanently discontinue the use of the affected CardioGen-82 generator if the incorrect solution is used to elute the generator.
Evaluate the patient’s radiation absorbed dose and monitor for the effects of radiation to critical organs such as bone marrow.
Excess Radiation Exposure with Failure to Follow the Eluate Testing Protocol
Excess radiation exposure occurs when the levels of Sr 82 or Sr 85 in the rubidium Rb 82 chloride injection exceed specified limits.

Record each generator eluate volume, including waste and test volumes, and keep a record of the cumulative eluate volume.
Strictly adhere to the generator eluate testing protocol, to minimize the risk of excess radiation exposure, including daily testing and additional testing at Alert Limits.
Stop using the generator if it reaches any of its Expiration Limits:

17 L for the generator’s cumulative eluate volume, or
42 days post generator calibration date, or
An eluate Sr 82 level of 0.01 ?Ci /mCi Rb 82, or
An eluate Sr 85 level of 0.1 ?Ci /mCi Rb 82

4 Contraindications

Addition of the following:

CardioGen-82 is contraindicated if a solution other than additive free 0.9% Sodium Chloride Injection USP has been used to elute the generator at any time. Immediately stop the patient infusion and permanently discontinue the use of the affected CardioGen-82 generator whenever the incorrect eluent is used.

5 Warnings and Precautions

Revised Subsection titles underlined below:

5.1 High Level Radiation Exposure with Use of Incorrect Eluent

Newly added information as below:

Use only additive free 0.9% Sodium Chloride Injection USP to elute the generator. Apply the provided saline tag to the additive free 0.9% Sodium Chloride Injection USP container before use. Additives present in other solutions (particularly calcium ions) expose patients to high levels of radiation by causing the release of large amounts of Sr 82 and Sr 85 into the eluate regardless of the generator’s age or prior use.

Immediately stop the patient infusion and discontinue use of the affected CardioGen-82 generator if the incorrect eluent is used and evaluate the patient’s radiation absorbed dose and monitor for the effects of radiation to critical organs such as bone marrow. When solutions containing calcium ions are used to elute the generator, high levels of radioactivity are present in any subsequent eluate, even with the use of additive free 0.9% Sodium Chloride Injection USP.

5.2 Excess Radiation Exposure with Failure to Follow Eluate Testing Protocol

Additions and/or revisions underlined:

Excess radiation exposure occurs when the Sr 82 and Sr 85 levels in rubidium Rb 82 chloride injections exceed the specified generator eluate limits.

Strictly adhere to the eluate testing protocol to minimize radiation exposure to the patient. Stop using the rubidium generator when the expiration limits are reached.

6 Adverse Reactions

Additions and/or revisions underlined:
Radiation Exposure

High level radiation exposure to the bone marrow has occurred in some patients due to Sr 82 and Sr 85 breakthrough in the eluate when an incorrect solution was used to elute the rubidium Rb 82 generator Excess radiation exposure has occurred …