Thallous Chloride, Tl 201

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 )

Injection: a clear, colorless solution available in the following strength at calibration time: 207.2 MBq (5.6 mCi) per 5.6 mL (37 MBq (1 mCi) per mL) in a multiple-dose vial Injection: available in the following strength at calibration time in a multiple-dose vial 207.2 MBq (5.6 mCi) per 5.6 mL (37 MBq (1 mCi) per mL) ( 3 )

None. None

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.

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.

Lactation: Temporarily discontinue breastfeeding. A lactating woman should pump and discard breast milk for at least 96 hours after Thallous Chloride Tl 201 Injection administration. ( 8.2 )

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.

8.2 Lactation Risk Summary Thallous chloride Tl 201 has been detected in the milk of lactating women. There are no data on the effects of thallous chloride Tl 201 on milk production or the effects of thallous chloride Tl 201 on the breastfed infant. Exposure of the breastfed infant to thallous chloride Tl 201 can be minimized by advising a lactating woman to temporarily discontinue breastfeeding and pump and discard milk for a minimum of 96 hours after administration of Thallous Chloride Tl 201 Injection. Minimize close contact with infants if the administered dose would result in an effective dose greater than 1 mSv to the infant. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for Thallous Chloride Tl 201 Injection and any potential adverse effects on the breastfed infant from Thallous Chloride Tl 201 Injection or from the underlying maternal condition.

8.4 Pediatric Use The safety and effectiveness of Thallous Chloride Tl 201 Injection in pediatric patients have not been established.

8.5 Geriatric Use Clinical studies of Thallous Chloride Tl 201 Injection for myocardial perfusion imaging did not include sufficient numbers of subjects aged younger than 65 years to determine whether they respond differently from younger subjects. Other reported experience has not revealed clinically relevant differences in the response of elderly in comparison to younger patients. This drug is known to be substantially excreted by the kidney, and the risk of toxic reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function.

Thallous chloride Tl 201 with no carrier added accumulates in viable myocardium in a manner analogous to that of potassium. Experiments in healthy subjects using labeled microspheres have shown that the myocardial distribution of thallous chloride Tl 201 correlates with regional perfusion. In clinical studies, Thallous Chloride Tl 201 images have been found to visualize areas of infarction as “cold” or nonlabeled regions that were confirmed by electrocardiographic and enzyme changes. Regions of transient myocardial ischemia corresponding to areas perfused by coronary arteries with partial stenoses have been visualized when Thallous Chloride Tl 201 Injection was administered in conjunction with an exercise stress test. Anatomic configurations may interfere with visualization of the right coronary artery territory.