RUBY-FILL

WARNING: HIGH LEVEL RADIATION EXPOSURE WITH USE OF INCORRECT ELUENT AND FAILURE TO FOLLOW QUALITY CONTROL TESTING PROCEDURE High Level Radiation Exposure with Use of Incorrect Eluent Patients are exposed to high radiation levels when the generator is eluted with the incorrect eluent due to high Sr 82 and Sr 85 breakthrough levels [see Warnings and Precautions ( 5.1 )] Use only additive-free 0.9% Sodium Chloride Injection USP to elute the generator [see Dosage and Administration ( 2.5 )] Immediately stop the patient infusion and discontinue the use of the affected RUBY-FILL (Rb 82) generator, if the incorrect solution is used to elute the generator [see Contraindications ( 4 )]. Evaluate the patient’s radiation absorbed dose and monitor for the effects of radiation to critical organs such as bone marrow [(see Dosage and Administration ( 2.9 )] . Excess Radiation Exposure with Failure to Follow Quality Control Testing Procedure Excess radiation exposure occurs when the levels of Sr 82 or Sr 85 in the rubidium Rb 82 chloride injection exceed specified limits [see Warnings and Precautions ( 5.2 )]. The system automatically generates a record and saves the data for each generator eluate volume, including flushing and test volumes. Total cumulative eluate volumes are also recorded and saved for the life of the generator [see Dosage and Administration ( 2.5 )] . Strictly adhere to the generator quality control testing procedure, to minimize the risk of excess radiation exposure, including daily testing and additional testing at Alert Limits [see Dosage and Administration ( 2.6 )] Stop use of a generator at any of the following Expiration Limits. Expiry Limits are: o 30 L for the generator's cumulative eluate volume, or o Expiration date of the generator (60 days post-calibration) o An eluate Sr 82 level of 0.01 mcCi /mCi (kBq/MBq) Rb 82, or o An eluate Sr 85 level of 0.1 mcCi /mCi (kBq/MBq) Rb 82 [see Dosage and Administration ( 2.7 )]. WARNING: HIGH LEVEL RADIATION EXPOSURE WITH USE OF INCORRECT ELUENT AND FAILURE TO FOLLOW QUALITY CONTROL TESTING PROCEDURE Please 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 ( 5.1 ) Use only additive-free 0.9% Sodium Chloride Injection USP to elute the generator ( 2.5 ) Immediately stop the patient infusion and discontinue the use of the affected RUBY-FILL generator if the incorrect solution is used to elute the generator ( 4 ) Evaluate the patient’s radiation absorbed dose and monitor for the effects of radiation to critical organs such as bone marrow ( 2.9 ) Excess Radiation Exposure with Failure to Follow the Quality Control Testing Procedure Excess-radiation exposure occurs when the levels of Sr 82 or Sr 85 in the Rubidium Rb 82 Chloride injection exceed specific limits. ( 5.2 ) Strictly adhere to the generator quality control testing procedure ( 2.6 ) Stop using the generator if it reaches any of its Expiration Limit ( 2.7 )

5 WARNINGS AND PRECAUTIONS •Pharmacologic induction of cardiovascular stress: May be associated with serious adverse reactions such as myocardial infarction, arrhythmia, hypotension, bronchoconstriction, 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 Use only additive-free 0.9% Sodium Chloride Injection USP to elute the generator. Apply the provided saline confirmation label to the additive-free 0.9% Sodium Chloride Injection USP bag 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 , 2.6 )] . Immediately stop the patient infusion and discontinue use of the affected RUBY-FILL 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 the eluate, even with the subsequent use of additive-free 0.9% Sodium Chloride Injection USP [see Boxed Warning, Dosage and Administration ( 2.9 ), and Contraindications ( 4 )]. 5.2 Excess Radiation Exposure with Failure to Follow the Quality Control Testing Procedure 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 quality control testing procedure to minimize radiation exposure to the patient. Stop using the rubidium generator when the expiration limits are reached [see Dosage and Administration ( 2.6 ) and ( 2.7 )]. 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 Radiation Risks RUBY-FILL use contributes to a patient’s overall long-term cumulative radiation exposure. Long-term cumulative radiation exposure is associated with an increased risk for cancer. Ensure safe handling to minimize radiation exposure to the patient and health care providers. Encourage patients to void as soon as a study is completed and as often as possible thereafter for at least one hour [see Dosage and Administration ( 2.1 ) and ( 2.2 )] .

6 ADVERSE REACTIONS To report SUSPECTED ADVERSE REACTIONS, contact Jubilant DraxImage Inc., dba Jubilant Radiopharma TM at 1-888-633-5343 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. The following serious adverse reaction associated with the use of rubidium Rb 82 chloride was identified in clinical trials or post marketing reports. 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, Warnings and Precautions ( 5.1 )] . Excess radiation exposure has occurred in some patients who received rubidium Rb 82 chloride injection at clinical sites where generator eluate testing appeared insufficient [see Boxed Warning, Warnings and Precautions ( 5.2 ), Dosage and Administration ( 2.6 )] .