THALLOUS CHLORIDE Tl 201

1 INDICATIONS AND USAGE Thallous Chloride Tl 201 Injection is indicated for use with planar scintigraphy or single-photon emission computed tomography (SPECT) for the following applications: Myocardial perfusion imaging in adults for the diagnosis of coronary artery disease by localization of: Non-reversible defects (myocardial infarction) Reversible defects (myocardial ischemia) when used in conjunction with exercise or pharmacologic stress Localization of sites of parathyroid hyperactivity pre- and post-operatively in adults with elevated serum calcium and parathyroid hormone levels Thallous Chloride Tl 201 Injection is a radioactive diagnostic drug indicated for use with planar scintigraphy or single-photon emission computed tomography (SPECT) for: Myocardial perfusion imaging in adults for the diagnosis of coronary artery disease by localization of: Non-reversible defects (myocardial infarction) Reversible defects (myocardial ischemia) when used in conjunction with exercise or pharmacologic stress Localization of sites of parathyroid hyperactivity pre- and post-operatively in adults with elevated serum calcium and parathyroid hormone levels ( 1 )

2 DOSAGE AND ADMINISTRATION • For myocardial perfusion imaging: Planar 37 MBq to 74 MBq (1 mCi to 2 mCi) ( 2.2 ) SPECT 74 MBq to 111 MBq (2 mCi to 3 mCi) ( 2.2 ) For localization of parathyroid hyperactivity, planar or SPECT: 75 MBq to 130 MBq (2 mCi to 3.5 mCi) Administer by intravenous injection. ( 2.2 ) See full prescribing information for administration and imaging instructions and radiation dosimetry information. ( 2.3 , 2.4 ) 2.1 Radiation Safety – Drug Handling Handle Thallous Chloride Tl 201 Injection with appropriate safety measures to minimize radiation exposure [see Warnings and Precautions ( 5.3 )] . Use waterproof gloves, effective radiation shielding, and other appropriate safety measures when preparing and handling Thallous Chloride Tl 201 Injection. Radiopharmaceuticals should be used by or under the control of 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 governmental agency authorized to license the use of radionuclides. 2.2 Recommended Dose Myocardial Perfusion Imaging in Adults Planar scintigraphy: 37 MBq to 74 MBq (1 mCi to 2 mCi) administered intravenously SPECT: 74 MBq to 111 MBq (2 mCi to 3 mCi) administered intravenously Parathyroid Hyperactivity Localization in Adults Planar or SPECT: 75 MBq to 130 MBq (2 mCi to 3.5 mCi) administered intravenously 2.3 Administration and Imaging Instructions Patient Preparation Instruct patients to hydrate before and after Thallous Chloride Tl 201 Injection administration and to void before imaging and frequently thereafter following Thallous Chloride Tl 201 Injection administration [see Warnings and Precautions ( 5.3 )] . Administration Use aseptic technique and radiation shielding when withdrawing and administering Thallous Chloride Tl 201 Injection. Visually inspect the drug for particulate matter and discoloration prior to administration, whenever the solution and container permit. Do not use if contents are turbid or discolored. Measure the patient dose with a dose calibrator immediately prior to administration. Use within 6 days from the manufacturer’s calibration date or 9 days from the date of manufacture, whichever comes first. Dispose of unused products in a safe manner in compliance with applicable regulations. Myocardial Perfusion Imaging For resting myocardial studies, begin imaging 10 minutes to 20 minutes after administration of Thallous Chloride Tl 201 Injection. Target-to-background ratios are improved when patients are injected upright and in the fasting state; the upright position reduces the hepatic and gastric thallium-201 concentration. For exercise stress testing, administer Thallous Chloride Tl 201 Injection at the start of a period of maximum stress, which is sustained for approximately 30 seconds after injection. Begin imaging within 10 minutes after administration to obtain maximum target-to-background ratios. Within 2 hours after the completion of the stress testing, the target-to-background ratios may decrease in lesions that are attributable to transient ischemia. Parathyroid Hyperactivity Localization For localization of parathyroid hyperactivity, administer Thallous Chloride Tl 201 Injection before, with, or after a minimal dose of a thyroid imaging agent such as sodium pertechnetate Tc 99m injection or sodium iodide I 123 capsules to enable thyroid subtraction imaging. 2.4 Radiation Dosimetry Estimated absorbed radiation doses from an intravenous injection of Thallous Chloride Tl 201 Injection are shown in Table 1. Table 1. Estimated Absorbed Radiation Dose per Injected Activity in Organs and Tissues of Adults from Intravenous Administration of Thallous Chloride Tl 201 Injection 1 Organ/ Tissue Absorbed Dose per Unit Activity Administered (mGy/MBq) Adrenals 0.063 Brain 0.057 Breasts 0.034 GB Wall 0.083 GI Tract LLI Wall 0.300 Small Intestine 0.379 Stomach 0.171 ULI Wall 0.297 Heart Wall 0.247 Kidneys 0.410 Liver 0.094 Lungs 0.047 Muscle 0.046 Ovaries 0.102 Pancreas 0.075 Red Marrow 0.044 Bone Surfaces 0.094 Skin 0.032 Spleen 0.166 Testes 0.209 Thymus 0.046 Thyroid 0.542 Urinary Bladder Wall 0.063 Uterus 0.086 Total Body 0.058 Effective Dose (mSv/MBq) 0.145 1 Assumed percentage of 98.3% thallium-201, 0.3% thallium-200, 1.2% thallium-202, and 0.2% lead-203 2.1 Radiation Safety – Drug Handling Handle Thallous Chloride Tl 201 Injection with appropriate safety measures to minimize radiation exposure [see Warnings and Precautions ( 5.3 )] . Use waterproof gloves, effective radiation shielding, and other appropriate safety measures when preparing and handling Thallous Chloride Tl 201 Injection. Radiopharmaceuticals should be used by or under the control of 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 governmental agency authorized to license the use of radionuclides. 2.2 Recommended Dose Myocardial Perfusion Imaging in Adults Planar scintigraphy: 37 MBq to 74 MBq (1 mCi to 2 mCi) administered intravenously SPECT: 74 MBq to 111 MBq (2 mCi to 3 mCi) administered intravenously Parathyroid Hyperactivity Localization in Adults Planar or SPECT: 75 MBq to 130 MBq (2 mCi to 3.5 mCi) administered intravenously 2.3 Administration and Imaging Instructions Patient Preparation Instruct patients to hydrate before and after Thallous Chloride Tl 201 Injection administration and to void before imaging and frequently thereafter following Thallous Chloride Tl 201 Injection administration [see Warnings and Precautions ( 5.3 )] . Administration Use aseptic technique and radiation shielding when withdrawing and administering Thallous Chloride Tl 201 Injection. Visually inspect the drug for particulate matter and discoloration prior to administration, whenever the solution and container permit. Do not use if contents are turbid or discolored. Measure the patient dose with a dose calibrator immediately prior to administration. Use within 6 days from the manufacturer’s calibration date or 9 days from the date of manufacture, whichever comes first. Dispose of unused products in a safe manner in compliance with applicable regulations. Myocardial Perfusion Imaging For resting myocardial studies, begin imaging 10 minutes to 20 minutes after administration of Thallous Chloride Tl 201 Injection. Target-to-background ratios are improved when patients are injected upright and in the fasting state; the upright position reduces the hepatic and gastric thallium-201 concentration. For exercise stress testing, administer Thallous Chloride Tl 201 Injection at the start of a period of maximum stress, which is sustained for approximately 30 seconds after injection. Begin imaging within 10 minutes after administration to obtain maximum target-to-background ratios. Within 2 hours after the completion of the stress testing, the target-to-background ratios may decrease in lesions that are attributable to transient ischemia. Parathyroid Hyperactivity Localization For localization of parathyroid hyperactivity, administer Thallous Chloride Tl 201 Injection before, with, or after a minimal dose of a thyroid imaging agent such as sodium pertechnetate Tc 99m injection or sodium iodide I 123 capsules to enable thyroid subtraction imaging. 2.4 Radiation Dosimetry Estimated absorbed radiation doses from an intravenous injection of Thallous Chloride Tl 201 Injection are shown in Table 1. Table 1. Estimated Absorbed Radiation Dose per Injected Activity in Organs and Tissues of Adults from Intravenous Administration of Thallous Chloride Tl 201 Injection 1 Organ/ Tissue Absorbed Dose per Unit Activity Administered (mGy/MBq) Adrenals 0.063 Brain 0.057 Breasts 0.034 GB Wall 0.083 GI Tract LLI Wall 0.300 Small Intestine 0.379 Stomach 0.171 ULI Wall 0.297 Heart Wall 0.247 Kidneys 0.410 Liver 0.094 Lungs 0.047 Muscle 0.046 Ovaries 0.102 Pancreas 0.075 Red Marrow 0.044 Bone Surfaces 0.094 Skin 0.032 Spleen 0.166 Testes 0.209 Thymus 0.046 Thyroid 0.542 Urinary Bladder Wall 0.063 Uterus 0.086 Total Body 0.058 Effective Dose (mSv/MBq) 0.145 1 Assumed percentage of 98.3% thallium-201, 0.3% thallium-200, 1.2% thallium-202, and 0.2% lead-203

4 CONTRAINDICATIONS None. None

5 WARNINGS AND PRECAUTIONS Hypersensitivity Reactions: Anaphylactic reactions characterized by cardiovascular, respiratory, and cutaneous symptoms may occur. Have resuscitation equipment and trained staff readily available. ( 5.1 ) Risk Associated with Stress Testing: Induction of cardiovascular stress may be associated with serious adverse reactions. Perform stress testing in a setting where cardiac resuscitation equipment and trained staff are readily available. ( 5.2 ) Radiation Risk: Ensure safe handling to minimize radiation exposure to patients and health care providers. ( 2.1 , 5.3 ) 5.1 Hypersensitivity Reactions Thallous Chloride Tl 201 Injection may cause anaphylactic reactions characterized by cardiovascular, respiratory, and cutaneous symptoms [see Adverse Reactions ( 6 )] . Have resuscitation equipment and trained staff readily available. 5.2 Risks Associated with Stress Testing Induction of cardiovascular stress might be associated with serious adverse reactions such as myocardial infarction, arrhythmia, hypotension or hypertension, ECG abnormalities, chest pain, bronchoconstriction, and cerebrovascular events [see Adverse Reactions ( 6 )] . Perform stress testing in the setting where cardiac resuscitation equipment and trained staff are readily available. Perform pharmacologic stress in accordance with the pharmacologic stress agent’s prescribing information. 5.3 Radiation Risk Thallous Chloride Tl 201 Injection contributes to a patient's overall long-term cumulative radiation exposure. Long-term cumulative radiation exposure is associated with an increased risk of cancer. Ensure safe handling to minimize radiation exposure to patients and health care providers. Advise patients to hydrate before and after administration and to void frequently after administration [see Dosage and Administration ( 2.1 , 2.3 )]. 5.4 Injection Site Reactions and Tissue Damage Injection site reactions and extravasation have been reported after administration of Thallous Chloride Tl 201 Injection [see Adverse Reactions ( 6 )] . Administer Thallous Chloride Tl 201 Injection strictly into the vein to avoid local tissue accumulation and irradiation. Confirm intravenous patency before injection.

6 ADVERSE REACTIONS The following clinically significant adverse reactions are described elsewhere in the labeling: Hypersensitivity Reactions [see Warnings and Precautions ( 5.1 )] Risk Associated with Stress Testing [see Warnings and Precautions ( 5.2 )] Injection Site Reactions and Tissue Damage [see Warnings and Precautions ( 5.4 )] The following adverse reactions associated with the use of Thallous Chloride Tl 201 Injection were identified in clinical studies or postmarketing reports. Because some of these reactions were 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: Cardiovascular, respiratory, and cerebrovascular disorders: myocardial infarction, arrhythmia, hypotension, bronchoconstriction, and cerebrovascular events in patients who have undergone stress testing Gastrointestinal disorders: nausea, vomiting, and diarrhea General disorders and administration site conditions: injection site reactions (burning, pain, redness, swelling, warmth, and tissue damage with chronic ulcer formation), chills, fever, and sweating Immune system disorders: hypersensitivity (anaphylaxis, hypotension, shortness of breath, pruritus, flushing, and diffuse rash) The following adverse reactions have been reported. In patients who have undergone stress testing: myocardial infarction, arrhythmia, hypotension, bronchoconstriction, and cerebrovascular events. Adverse reactions in other patients: nausea, vomiting, diarrhea, injection site reactions, chills, fever, sweating, hypersensitivity (anaphylaxis, hypotension, shortness of breath, pruritus, flushing, diffuse rash). ( 6 ) To report SUSPECTED ADVERSE REACTIONS, contact Curium US LLC at 1-866-789-2211 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

8.1 Pregnancy Risk Summary There are no data on Thallous Chloride Tl 201 Injection use in pregnant women to evaluate for a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes. Studies using human placentas demonstrate that thallous chloride Tl 201 crosses the placenta. No animal reproductive studies have been conducted. All radiopharmaceuticals, including Thallous Chloride Tl 201 Injection have the potential to cause fetal harm depending on the fetal stage of development and the magnitude of the radiation dose. If considering administration of Thallous Chloride Tl 201 Injection to a pregnant woman, inform the patient about the potential for adverse pregnancy outcomes based on the radiation dose from Thallous Chloride Tl 201 Injection and gestational timing of exposure. The background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defects, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 3% and 10% to 20%, respectively.