Cardiogen 82 Drug Information

CardioGen-82, used to produce Rubidium Chloride Rb 82 Injection, is indicated for positron emission tomography (PET) of the myocardium under rest or pharmacologic stress conditions to evaluate regional myocardial perfusion in adult patients with suspected or existing coronary artery disease.

Radiation Safety - Drug Handling CardioGen-82, when eluted with additive-free 0.9% Sodium Chloride Injection, produces Rubidium Chloride Rb 82 Injection. Handle CardioGen-82, Rubidium Chloride Rb 82 Injection, and Infusion Systems with appropriate safety measures to minimize radiation exposure. Wear waterproof gloves and effective shielding throughout the entire preparation and handling.

Limit the use of radiopharmaceuticals to healthcare providers who are qualified by specific training and experience in the safe use and handling of radionuclides and whose experience and training have been approved by the appropriate government agency authorized to license the use of radionuclides.

Dosing and Administration of Rubidium Chloride Rb 82 Injection Dosing The recommended dose of Rubidium Chloride Rb 82 Injection per rest or stress component of a PET MPI procedure in adults is 10 MBq/kg to 30 MBq/kg actual body weight (0.27 mCi/kg to 0.81 mCi/kg) administered by intravenous infusion at 50 mL/minute or 20 mL/minute through a catheter inserted into a large peripheral vein. Do not exceed a maximum dose of 2,220 MBq (60 mCi) or a maximum volume of 100 mL per rest or stress component of a procedure. Administration Instructions Observe aseptic techniques in all drug handling and administration.

Use CardioGen-82 with the CardioGen-82 Model 1700 Infusion System to elute and administer Rubidium Chloride Rb 82 Injection. Use the lowest dose necessary, consistent with the goal of as low as reasonably achievable (ALARA), to obtain adequate cardiac visualization based on patient body weight and the imaging equipment and acquisition methodology used to perform the procedure. For example, 3D image acquisition may require doses at the lower end of the recommended range, compared to 2D imaging.

Administer two single doses to complete rest and stress myocardial perfusion imaging (MPI). The minimum interval between the rest and stress doses is 10 minutes to allow sufficient Rb 82 decay. Instruct patients to void as soon as a study is completed and as often as possible thereafter for at least one hour.

Image Acquisition Instructions Rest Imaging Administer a single dose of Rubidium Chloride Rb 82 Injection. Start imaging 60 seconds to 90 seconds after completion of the first dose infusion and acquire images for 5 minutes. Stress Imaging Begin the study at least 10 minutes after completion of the resting dose infusion, to allow for sufficient Rb 82 decay.

Administer a pharmacologic stress agent in accordance with its prescribing information. After the administration of the pharmacologic stress agent, administer the second dose of Rubidium Chloride Rb 82 Injection at the time interval according to the prescribing information of the pharmacologic stress agent. Rest and Stress Imaging If a longer circulation time is anticipated (e.g., in a patient with severe left ventricular dysfunction), start imaging 120 seconds after the dose.

Acquisition may be started immediately post-injection if dynamic imaging is needed.

Infusion System Use

CardioGen-82 only with the CardioGen-82 Infusion System Model 1700, which is specifically designed for use with the generator and capable of accurate measurement and delivery of doses of Rubidium Chloride Rb 82 Injection. Follow instructions in the CardioGen-82 Infusion System Model 1700 Operator’s Manual for the setup and administration of Rubidium Chloride Rb 82 Injection.

Directions for Eluting Rubidium Chloride Rb 82 Injection

Use only additive-free 0.9% Sodium Chloride Injection to elute the generator. Prepare the 0.9% Sodium Chloride Injection for use with the Saline Tag. Prepare the intravenous port in accordance with the approved prescribing information of the 0.9% Sodium Chloride Injection.

The intravenous administration port of the 0.9% Sodium Chloride Injection container must be penetrated only one time. Strap the saline tag provided with the CardioGen-82 Infusion System on the additive-free 0.9% Sodium Chloride Injection container and install on the CardioGen-82 Infusion System. Once the container port closure is penetrated, it should remain installed on the CardioGen-82 Infusion System for its entire period of use.

A maximum of 12 hours from the initial port closure penetration is permitted, after which the bag must be replaced for the next patient. Allow at least 10 minutes between elutions for regeneration of Rb 82. The system automatically discards the first 50 mL of eluate each day the generator is eluted and records and saves all eluate volumes (all flushing, quality control (QC) testing, and patient infusions), representing the cumulative volume of eluate each day the generator is eluted.

Perform eluate testing according to the Eluate Testing Protocol. Stop using the generator when the expiration limits are reached. The maximum available activity of Rb 82 (dose delivery limit) will decrease as the generator ages.

Observe aseptic technique throughout. Follow all instructions in the CardioGen-82 Infusion System Model 1700 Operator’s Manual for performing all eluate testing as described. Mandatory Eluate Testing Perform Mandatory Eluate Testing to determine Rb 82, Sr 82, and Sr 85 levels (see Daily Quality Control Procedure): Daily – Before administering Rubidium Chloride Rb 82 Injection to the first patient each day.

Repeat as indicated after an Alert Limit has been detected. Once an Alert Limit has been reached, the system will require additional eluate testing at intervals determined by the day’s elution volume and enforced by the system software. Specifically, the infusion system will require the user to perform additional eluate testing after each 750 mL of elution volume when any Alert Limit parameter has been reached.

Infusion System Calibration Before administering Rubidium Chloride Rb 82 Injection to the first patient, perform the Rubidium Chloride Rb 82 Injection Dose Calibration using an external dose calibrator at the following times (see Calibration Procedure): After installation of a new generator After installation of a new CardioGen-82 Accessory Package, Item # 001710 Every 14 days Calibration Procedure Set a dose calibrator for Rb 82 as recommended by the manufacturer. Obtain the reading from the instrument in millicuries. Following the prompts in the Graphical User Interface (GUI) for the CardioGen-82 Infusion System Model 1700, elute the generator with additive-free 0.9% Sodium Chloride Injection at a rate of 50 mL/min and collect the eluate in the stoppered vial specifically provided for use with the CardioGen-82 Infusion System Model 1700 (alternative vials, glass or plastic are not suitable).

Note the exact time of end of elution (EOE). Using the external dose calibrator, assay the eluate at exactly 2:30, 3:45, or 5:00 minutes after EOE. Following the prompts in the GUI for the CardioGen-82 Infusion System Model 1700, enter the Rb 82 reading from the dose calibrator and the time since EOE.

The infusion system software will automatically calculate the Calibration Ratio. If the ratio is within +/- 2% (0.98 to 1.02), the infusion system will allow acceptance of the calibration factor that was used for the elution. Repeat steps 1 through 4 for a flow rate of 20 mL/min.

Daily Quality Control Procedure Each day, before administering Rubidium Chloride Rb 82 Injection, perform the following testing: Place the stoppered vial into the Sr detector well. Following the GUI prompts, initiate the Daily Quality Control workflow. The infusion system will automatically perform the Sr Detector Background Reading.

The infusion system will automatically perform the Generator Column Wash. Strontium Level Test and Dose Constancy: The infusion system will elute the generator with 50 mL of additive-free 0.9% Sodium Chloride Injection at a rate of 50 mL/min into the stoppered vial. The Sr detector measures the Rb 82 and strontium in the 50 mL elution.

Using the Rb 82 and strontium measurements, the infusion system software will automatically calculate microCi Sr 82/mCi Rb 82 and microCi Sr 85/mCi Rb 82. The GUI will automatically indicate if the results exceed Alert or Expiration Limits. The infusion system software will automatically calculate Dose Constancy.

Constancy Check of the Sr detector: The GUI will prompt the user to perform the constancy check of the Sr detector. Place the external constancy source in the detector well of the infusion system. The infusion system software will automatically calculate the constancy of the Sr detector versus the external constancy source when instructed.

Expiration Limits of CardioGen-82 The CardioGen-82 Infusion System Model 1700 software will automatically indicate and will stop use of CardioGen-82 once any one of the following Expiration Limits is reached. Certain doses, including the maximum recommended dose of 2,220 MBq (60 mCi), may not be achievable for the entire shelf-life of the generator.

The following clinically significant adverse reactions are described elsewhere in the labeling: High Level Radiation Exposure with Use of Incorrect Eluent Excess Radiation Exposure with Failure to Follow Eluate Testing Protocol The following serious adverse reactions have been identified during post-approval use of CardioGen-82. 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. Radiation Exposure High level radiation exposure to the bone marrow from using an incorrect eluent.

Excess radiation exposure due to insufficient eluate testing. To report SUSPECTED ADVERSE REACTIONS, contact Bracco Diagnostics Inc. at 1-800-257-8151 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

Pregnancy Risk Summary There are no data available on the use of rubidium chloride Rb 82 in pregnant women. Animal reproductive studies have not been conducted with rubidium chloride Rb 82. However, all radiopharmaceuticals, including Rubidium Chloride Rb 82 Injection generated by CardioGen-82, have the potential to cause fetal harm depending on the fetal stage of development and the magnitude of the radiation dose.

If considering Rubidium Chloride Rb 82 Injection administration to a pregnant woman, inform the patient about the potential for adverse pregnancy outcomes based on the radiation dose from rubidium-82 (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 respectively.

Pediatric Use The safety and effectiveness of CardioGen-82, used to produce Rubidium Chloride Rb 82 Injection, in pediatric patients have not been established.