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

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.

12.3 Pharmacokinetics Distribution After intravenous administration, thallous chloride Tl 201 clears from the blood with maximal concentration in normal myocardium occurring at about 10 minutes. It will, in addition, localize in parathyroid adenomas; it is not specific since it will localize to a lesser extent in sites of parathyroid hyperplasia and other abnormal tissues such as thyroid adenoma, neoplasia (e.g., parathyroid carcinoma), and sarcoid. Biodistribution is generally proportional to organ blood flow at the time of injection. Blood clearance of thallous chloride Tl 201 is primarily by the myocardium, thyroid, liver, kidneys, and stomach with the remainder distributing fairly uniformly throughout the body. The dosimetry data in Table 1 reflect this distribution pattern and are based on a biological half-life of 2.4 days. Elimination Five minutes after intravenous administration only 5% to 8% of injected activity remained in the blood. A biexponential disappearance curve was obtained, with 91.5 % of the blood radioactivity disappearing with a half-time of about 5 minutes. The remainder had a half-time of about 40 hours. Excretion Approximately 4% to 8% of the injected dose was excreted in the urine in the first 24 hours. The whole body disappearance half-time was 9.8 ± 2.5 days. Kidney concentration was found to be about 3% of the injected activity and the testicular content was 0.15%. Net thyroid activity was determined to be only 0.2% of the injected dose, and the activity disappeared in 24 hours. From anterior and posterior whole-body scans, it was determined that about 45% of the injected dose was in the large intestines and contiguous structures (liver, kidneys, abdominal musculature).