THALLOUS CHLORIDE TL 201

11.1 Drug Characteristics Thallous Chloride Tl 201 Injection is a sterile, radioactive diagnostic drug for intravenous use. Each mL contains 37 MBq (1 mCi) thallous chloride Tl 201 at calibration time and the following inactive ingredients: 9 mg sodium chloride and 0.9% (v/v) benzyl alcohol. The pH is adjusted to between 4.5 to 7.0 with hydrochloric acid and/or sodium hydroxide. Thallium-201 is cyclotron produced. At the time of calibration it contains no more than 1% thallium-200, no more than 1% thallium-202, no more than 0.25% lead-203, and no less than 98% thallium-201 as a percentage of total activity. No carrier has been added. The concentration of each radionuclidic contaminant changes with time. Figure 1 shows maximum concentration of thallium-200 (Tl 200) and thallium-202 (Tl 202) radionuclidic contaminants as a function of time. Figure 1. Radionuclidic Contaminants figure 1 11.2 Nuclear Physical Characteristics Thallium-201, with a physical half-life of 72.9 hours, decays by electron capture to mercury-201. Photons that are useful for detection and imaging are listed in Table 2. The lower energy x-rays obtained from the mercury-201 daughter of thallium-201 are recommended for myocardial imaging, because the mean percent disintegration at 68.9 to 80.3 keV is much greater than the combination of gamma-4 and gamma-6 mean percent disintegration. Table 2. Principal Radiation Emission Data Radiation Mean Percent/ Disintegration Energy (keV) Gamma-4 2.7 135.3 Gamma-6 10.0 167.4 Mercury x-rays 94.4 68.9-80.3 The specific gamma ray constant for thallium-201 is 0.45 R/mCi-hr at 1 cm. The first half-value thickness of lead (Pb) is 0.026 cm. A range of values for the relative attenuation of the radiation emitted by this radionuclide that results from interposition of various thicknesses of Pb is shown in Table 3. For example, the use of 0.194 cm of lead will decrease the external radiation exposure by a factor of about 1,000. Table 3. Radiation Attenuation by Lead Shielding cm of Lead (Pb) Coefficient of Attenuation 0.026 0.5 0.052 10 -1 0.089 10 -2 0.194 10 -3 0.310 10 -4 To correct for physical decay of the radionuclide, the fractions that remain at selected intervals after calibration time are shown in Table 4. Table 4. Physical Decay Chart for Thallium-201; Half-Life 72.9 Hours Hours Fraction Remaining Hours Fraction Remaining 0* 1 66 0.53 6 0.95 72 0.50 12 0.89 78 0.48 18 0.84 84 0.45 24 0.80 90 0.43 30 0.75 96 0.40 36 0.74 108 0.36 42 0.67 120 0.32 48 0.63 132 0.29 54 0.60 144 0.25 60 0.57 * Calibration Time

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 )

• 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

None. None

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.