CARDIOGEN-82 Solution for injection Ref.[10196] Active ingredients: Rubidium ⁸²Rb chloride

5.1 High Level Radiation Exposure with Use of Incorrect Eluent

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 [Dosage and Administration (2.1, 2.5, and 2.6, 2.7)].

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 [see Boxed Warning, Dosage and Administration (2.10) and Contraindications (4)].

5.2 Excess Radiation Exposure with Failure to Follow Eluate Testing Protocol

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 [see Dosage and Administration (2.6, 2.7) and (2.8)].

5.3 Risk 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 Volume Overload

Patients with congestive heart failure or the elderly may experience a transitory increase in circulatory volume load.

5.5 Cumulative Radiation Exposure: Long-Term Risk of Cancer

Rubidium Rb 82 chloride injection, similar to other radiopharmaceuticals, 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 Rb 82 chloride injection necessary for imaging and ensure safe handling to protect the patient and health care worker [see Dosage and Administration (2.1) and (2.2)]. Encourage patients to void as soon as a study is completed and as often as possible thereafter for a least one hour.

The following serious adverse reactions have been identified during postapproval 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 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 [see Boxed Warning and Warnings and Precautions (5.1)].

Excess radiation exposure has occurred in some patients who received rubidium Rb 82 chloride injections at clinical sites where generator eluate testing appeared insufficient [see Boxed Warning, Warnings and Precautions (5.2), and Dosage and Administration (2.6 or 2.7)].

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.

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 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.

Rubidium Rb 82 chloride injection safety and effectiveness in pediatric patients have not been established.

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 [see Warnings and Precautions (5.4)].

Reductions in renal function are not anticipated to alter clearance of rubidium Rb 82 chloride injection because Rb 82 decays to stable Kr-82 with a half-life of 75 seconds and Kr-82 is exhaled through the lungs.

Reductions in hepatic function are not anticipated to alter clearance of rubidium Rb 82 chloride injection.