Rubidium Chloride Rb-82

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. CardioGen-82, used to produce Rubidium Chloride Rb 82 Injection, is a radioactive diagnostic agent 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. ( 1 )

Rubidium Rb 82 generator used to produce Rubidium Chloride Rb 82 Injection: strontium-82 (Sr 82), with an activity of 3,330 MBq to 5,550 MBq (90 mCi to 150 mCi) at calibration time, adsorbed on a hydrous stannic oxide column. Rubidium Rb 82 generator used to produce Rubidium Chloride Rb 82 Injection: 3,330 MBq to 5,550 MBq (90 mCi to 150 mCi) of strontium-82 (Sr 82) at calibration time, adsorbed on a hydrous stannic oxide column. ( 3 )

None. None. ( 4 )

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 )] .

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 .

Lactation: Do not resume breastfeeding until at least one hour after administration of Rubidium Chloride Rb 82 Injection. ( 8.2 )

8.1 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 2% to 4% and 15% to 20%, respectively.

8.2 Lactation Risk Summary There is no information regarding the presence of rubidium chloride Rb 82 in human milk, the effects on the breastfed infant or the effects on milk production. Due to the short half-life of 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 Chloride Rb 82 Injection, any potential adverse effects on the breastfed child from Rb 82 or from the underlying maternal condition. Clinical Considerations Exposure to Rb 82 through breast milk can be minimized if breastfeeding is discontinued when Rubidium Chloride Rb 82 Injection is administered. Do not resume breastfeeding until at least one hour after administration of Rubidium Chloride Rb 82 Injection.

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

8.5 Geriatric Use In elderly patients with a clinically important decrease in cardiac function, lengthen the delay between infusion and image acquisition [see Dosage and Administration ( 2.3 )]. Observe for the possibility of fluid overload.

Rb 82 is analogous to potassium ion (K + ) in its biochemical behavior and is extracted by the myocardium in proportion to the blood flow. Rb + participates in the sodium-potassium (Na + /K + ) ion exchange pumps that are present in cell membranes. The intracellular uptake of Rb 82 requires maintenance of ionic gradient across cell membranes. Rb 82 radioactivity is increased in viable myocardium reflecting intracellular retention, while the tracer is cleared from necrotic or infarcted tissue.