CardioGen-82

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 strontium (Sr) 82 and Sr 85 breakthrough levels. Use only additive-free 0.9% Sodium Chloride Injection to elute the generator. If an incorrect solution is used to elute the CardioGen-82 generator: 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 the use of the affected generator [see Dosage and Administration (2.5) and Warnings and Precautions (5.1) ]. 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 Chloride Rb 82 Injection exceed specified limits. 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 60 days post generator calibration date An eluate Sr 82 level of 0.01 microCi /mCi Rb 82 An eluate Sr 85 level of 0.1 microCi /mCi Rb 82 [see Dosage and Administration ( 2.5 , 2.6 , 2.7 , 2.8 ) and Warnings and Precautions ( 5.2 )] WARNING: HIGH LEVEL RADIATION EXPOSURE WITH USE OF INCORRECT ELUENT and FAILURE TO FOLLOW THE ELUATE TESTING PROTOCOL See full prescribing information for complete boxed warning. High Level Radiation Exposure with Use of Incorrect Eluent Using the incorrect eluent can cause high Strontium (Sr) 82 and Sr 85 breakthrough levels. Use only additive-free 0.9% Sodium Chloride Injection to elute CardioGen-82. If an incorrect solution is used to elute CardioGen-82: 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 generator. ( 2.5 , 2.9 , 5.1 ) 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 Chloride Rb 82 Injection exceed limits. Strictly adhere to the generator eluate testing protocol. Stop using the generator if it reaches any of its Expiration Limits. ( 2.5 , 2.6 , 2.7 , 5.2 )

5 WARNINGS AND PRECAUTIONS Risk Associated with Pharmacological Stress: Pharmacologic induction of cardiovascular stress may cause serious adverse reactions such as myocardial infarction, arrhythmia, hypotension, broncho-constriction, and cerebrovascular events. Perform testing only in setting where cardiac resuscitation equipment and trained staff are readily available. ( 5.3 ) 5.1 High Level Radiation Exposure with Use of Incorrect Eluent 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 )] . 5.2 Excess Radiation Exposure with Failure to Follow the Eluate Testing Protocol Excess radiation exposure occurs when the Sr 82 and Sr 85 levels in the Rubidium Chloride Rb 82 Injection exceed the specified generator eluate limits. Strictly adhere to the eluate testing protocol to minimize radiation exposure to the patient. Stop using the CardioGen-82 generator when the expiration limits are reached [see Dosage and Administration ( 2.6 , 2.7 , 2.8 )]. 5.3 Risks Associated with Pharmacologic Stress Pharmacologic induction of cardiovascular stress may be associated with serious adverse reactions such as myocardial infarction, arrhythmia, hypotension, bronchoconstriction, and cerebrovascular events. Perform pharmacologic stress testing in accordance with the pharmacologic stress agent’s prescribing information and only in the setting where cardiac resuscitation equipment and trained staff are readily available. 5.4 Cumulative Radiation Exposure: Long-Term Risk of Cancer Rubidium chloride Rb 82 contributes to a patient’s overall long-term cumulative radiation exposure. Long-term cumulative radiation exposure is associated with an increased risk of cancer. Use the lowest dose of Rubidium Chloride Rb 82 Injection necessary for imaging and ensure safe handling to protect the patient and health care providers . Encourage patients to void as soon as a study is completed and as often as possible thereafter for a least one hour [see Dosage and Administration ( 2.1 , 2.2 )] .

6 ADVERSE REACTIONS 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 )] 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 .