THALLOUS CHLORIDE TL 201- thallous chloride, tl 201 injection, solution

THALLOUS CHLORIDE Tl 201 by

Drug Labeling and Warnings

THALLOUS CHLORIDE Tl 201 by is a Prescription medication manufactured, distributed, or labeled by Curium US LLC. Drug facts, warnings, and ingredients follow.

Drug Details [pdf]

  • 1 INDICATIONS AND USAGE

    Thallous Chloride Tl 201 Injection is a diagnostic radiopharmaceutical indicated for

    • Myocardial perfusion imaging with planar scintigraphy or single-photon emission computed tomography (SPECT)  for the diagnosis of coronary artery disease by localization of:
      • Non-reversible defects (myocardial infarction) which may have prognostic value regarding survival.
      • Reversible defects (myocardial ischemia) when used in conjunction with exercise or pharmacologic stress.
    • Localization of sites of parathyroid hyperactivity pre- and post-operatively in patients with elevated serum calcium and parathyroid hormone levels.
  • 2 DOSAGE AND ADMINISTRATION

    2.1 Radiation Safety

    Thallous Chloride Tl 201 Injection emits radiation and must be handled with appropriate safety measures and in accordance with the “as low as reasonably achievable” (ALARA) principle of radioactivity dosing.

    Use the lowest dose of Thallous Chloride Tl 201 Injection necessary to obtain the intended diagnostic image. Individualize the dose and consider factors such as body size, and the equipment and technique to be employed. 

    2.2 Recommended Dose

    Myocardial perfusion

    • Planar scintigraphy: 37 to 74 MBq (1 to 2 mCi) administered intravenously
    • SPECT: 74 to 111 MBq (2 to 3 mCi) administered intravenously

    Parathyroid hyperactivity localization

    Planar or SPECT: 75 to 130 MBq (2 to 3.5 mCi) administered intravenously

    2.3 Drug Administration and Imaging

    For resting myocardial studies, begin imaging 10 to 20 minutes after injection of Thallous Chloride Tl 201. Myocardial-to-background ratios are improved when patients are injected upright and in the fasting state; the upright position reduces the hepatic and gastric thallium Tl-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 ten minutes after administration to obtain maximum target-to-background ratios. Within two hours after the completion of the stress testing the target-to-background ratios may decrease in lesions that are attributable to transient ischemia.

    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 or sodium iodide I-123 to enable thyroid subtraction imaging. 

    2.4 Radiation Dosimetry

    The estimated absorbed radiation doses at calibration time to a 70 kg patient from an intravenous injection of Thallous Chloride Tl 201 are shown in Table 1. The estimates were calculated based on human data from Krahwinkel et al.1and Thomas et al.2Assumed percentages of 98.3% 201Tl, 0.3% 200Tl, 1.2% 202Tl, and 0.2% 203Pb. The effective dose was calculated using ICRP 103 tissue weighting factors and assumptions on the biodistribution data based on data from Krahwinkel et al. and Thomas et al.

    Table 1. Radiation Dose Estimates for Thallous Chloride Tl 201  (includes contaminants)

    Organ

    Estimated Radiation Dose

    mGy/MBq

    rad/mCi

    Adrenals

    6.33E-02

    2.34E-01

    Brain

    5.68E-02

    2.10E-01

    Breasts

    3.39E-02

    1.25E-01

    GB Wall  

    8.31E-02

    3.07E-01

    LLI Wall

    2.96E-01

    1.09E+00

    Small Intestine

    3.79E-01

    1.40E+00

    Stomach

    1.71E-01

    6.34E-01

    ULI Wall

    2.97E-01

    1.10E+00

    Heart Wall

    2.47E-01

    9.14E-01

    Kidneys

    4.10E-01

    1.52E+00

    Liver

    9.39E-02

    3.47E-01

    Lungs

    4.73E-02

    1.75E-01

    Muscle

    4.59E-02

    1.70E-01

    Ovaries

    1.02E-01

    3.76E-01

    Pancreas

    7.52E-02

    2.78E-01

    Red Marrow

    4.44E-02

    1.64E-01

    Bone Surfaces

    9.37E-02

    3.47E-01

    Skin

    3.16E-02

    1.17E-01

    Spleen

    1.66E-01

    6.14E-01

    Testes 

    2.09E-01

    7.73E-01

    Thymus

    4.60E-02

    1.70E-01

    Thyroid

    5.42E-01

    2.00E+00

    Urinary Bladder Wall   

    6.25E-02

    2.31E-01

    Uterus

    8.63E-02

    3.19E-01

    Total Body

    Effective Dose

    5.77E-02

    0.145mSv/MBq

    2.14E-01

    0.535rem/mCi

    2.5 Drug Handling

    • Do not use this drug after six (6) days from the calibration date, or nine (9) days from date of manufacture, whichever comes first.
    • Limit the use of this drug, to physicians who are qualified by training and experience in the safe use and handling of radionuclides.
    • Wear waterproof gloves during the handling procedures.
    • Aseptically withdraw the material for use with a shielded sterile syringe.
    • Measure the patient dose with a suitable radioactivity calibration system immediately prior to administration.
    • Visually inspect the drug for particulate matter and discoloration prior to administration, whenever solution and container permit.  Do not use if contents are turbid.
    • Minimize radiation exposure to the patient and ensure minimum radiation exposure to occupational workers.
       
  • 3 DOSAGE FORMS AND STRENGTHS

    Thallous Chloride Tl 201 Injection is supplied as a sterile, non-pyrogenic solution for intravenous administration.

    Table 2. Strengths Available

    Total Radioactivity* per Vial
    (*At time of calibration)

    MBq

    mCi

    103.6

    2.8

    207.2

    5.6

    233.1

    6.3

    366.3

    9.9
  • 4 CONTRAINDICATIONS

    None. 

  • 5 WARNINGS AND PRECAUTIONS

    5.1 Anaphylactoid Reactions

    Anaphylactoid reactions (hypotension, pruritus, flushing, and diffuse rash) have been reported.

    5.2 Risks Associated with Stress Testing

    Perform stress testing only under the supervision of a qualified physician and in a laboratory equipped with appropriate resuscitation and support equipment. Patients suspected or known to have myocardial infarction or ischemia, require continuous clinical monitoring and treatment in accordance with safe, accepted procedures.

    Induction of cardiovascular stress might be associated with serious adverse events such as myocardial infarction, arrhythmia, hypotension or hypertension, ECG abnormalities, chest pain,  bronchoconstriction, and cerebrovascular events. Perform pharmacologic stress when indicated and in accordance with the pharmacologic stress agent’s prescribing information.

    5.3 Radiation Risks

    Thallous Chloride Tl 201 contributes to the cumulative radiation exposure. When considering administration of Thallous Chloride Tl 201 Injection to women of child-bearing potential, consider the radiation risks for a fetus [see Use in Specific Populations (8.1)].

    Use the lowest dose necessary for imaging and ensure safe handling to protect the patient and health care worker [see Dosage and Administration (2.1)(2.5)].

    5.4 Risk of Extravasation and Tissue Damage

    Inject Thallous Chloride Tl 201 strictly intravenously to avoid local tissue accumulation and irradiation. Confirm intravenous patency before injection  [see Adverse Reactions (6.3)].

  • 6 ADVERSE REACTIONS

    6.1 Serious Reactions

    • Anaphylactoid Reactions
      Following the administration of Thallous Chloride Tl 201 Injection, anaphylactoid reactions  have been reported (characterized by cardiovascular, respiratory and cutaneous symptoms), some considered serious and severe enough to require treatment. Hypotension, pruritus, flushing, and diffuse rash which responds to antihistamines have been reported.
    • Stress Testing
      Serious reactions reported in patients who have undergone  stress testing include  myocardial infarction, arrhythmia, hypotension, bronchoconstriction, and cerebrovascular events [see Warnings (5)]. 

    6.2 Common Reactions

    The most frequently reported reactions were itching, nausea, vomiting, mild diarrhea, tremor, shortness of breath, chills, fever, conjunctivitis, sweating, and blurred vision.

    6.3 Postmarketing Experience

    The following adverse reactions have been identified during post-approval use of Thallous Chloride Tl 201.  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:

    Injection site reactions and extravasation of Tl-201 have been reported:  burning, pain, redness, swelling, warmth, and, in one case, tissue damage with chronic ulcer formation

  • 7 DRUG INTERACTIONS

    Drugs that increase or decrease myocardial blood flow or potassium uptake might correspondingly alter the biodistribution of Thallous Chloride Tl 201.

  • 8 USE IN SPECIFIC POPULATIONS

    8.1 Pregnancy Category C

    There are no adequate or well-controlled studies of Thallous Chloride Tl 201 Injection use in pregnant women. Studies using human placentas demonstrate that Thallous Chloride Tl 201 crosses the placenta. Animal reproductive studies have not been conducted. Administer Thallous Chloride Tl 201 Injection to a pregnant woman only if clearly needed.

    8.3 Nursing Mothers

    Thallous Chloride Tl 201 is excreted in human milk. Advise patients who continue to breastfeed to express and discard milk for a minimum of 2 weeks after administration of Thallous Chloride Tl 201. Minimize close contact with infants if the administered dose would result in an effective dose greater than 1 mSv (0.1 rem) to the infant.

    8.4 Pediatric Use

    Safety and effectiveness of Thallous Chloride Tl 201 Injection in pediatric patients have not been established.

    8.6 Females of Reproductive Potential

    Assess the pregnancy status of women of childbearing potential prior to performing imaging procedures with Thallous Chloride Tl 201 Injection [see Warnings and Precautions (5.3)].

  • 10 OVERDOSAGE

    In the event of the administration of a radiation overdose with Thallous Chloride Tl 201, the absorbed dose to the patient should be reduced where possible by increasing the elimination of the radionuclide from the body by forced diuresis with frequent voiding and stimulation of the gastrointestinal passage.

  • 11 DESCRIPTION

    11.1 Chemical Characteristics

    Thallous Chloride Tl 201 Injection is supplied in an isotonic solution as a sterile, non-pyrogenic diagnostic radiopharmaceutical for intravenous administration. Each milliliter contains 37 MBq (1 mCi) Thallous Chloride Tl 201 at calibration time, made isotonic with 9 milligrams sodium chloride and preserved with 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 Tl-201 is cyclotron produced. At the time of calibration it contains no more than 1.0% thallium Tl-200, no more than 1.0% thallium Tl-202, no more than 0.25% lead Pb-203, and no less than 98% thallium Tl-201 as a percentage of total activity. No carrier has been added.

    It is recommended to administer Thallous Chloride Tl 201  Injection close to calibration time to minimize the effect of higher levels of radionuclidic contaminants present at pre- and post-calibration dates. The concentration of each radionuclidic contaminant changes with time. Figure 1 shows maximum concentration of each radionuclidic contaminant as a function of time.

    Figure 1. Radionuclidic Contaminants

    figure 1

    11.2 Physical Characteristics

    Thallium Tl-201, with a physical half-life of 72.9 hours, decays by electron capture to mercury Hg-201. Photons that are useful for detection and imaging are listed in Table 3. The lower energy x-rays obtained from the mercury Hg-201 daughter of thallium Tl-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 3. 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

    From: Stabin MG, da Luz CQPL. New Decay Data for Internal and External Dose Assessment, 2002, Health Phys. 83(4):471-4753.

    11.3 External Radiation

    The specific gamma ray constant for thallium Tl-201 is 4.64 R/mCi-hr at 1 cm. The first half-value thickness of lead (Pb) is 0.0006 cm. A range of values for the radiation emitted by this radionuclide with the corresponding exposure rate at 1 cm that results from interposition of various thicknesses of lead is shown in Table 4. For example, the use of 0.21 cm of lead will decrease the external radiation exposure by a factor of about 1,000.

    Table 4. Radiation Attenuation by Lead Shielding

    cm of
    Lead (Pb)

    Coefficient of

    Attenuation

    0.0005

    0.5

    0.026

    10-1

    0.081

    10-2

    0.18

    10-3

    0.31

    10-4

    Data supplied by Oak Ridge Associated Universities, Radiopharmaceutical Internal Dose Information Center, Oak Ridge, TN, 1994. Includes 10 keV x-rays4.

    To correct for physical decay of the radionuclide, the fractions that remain at selected intervals after calibration time are shown in Table 5.

    Table 5. Thallous Chloride Tl 201 Decay Chart; Half-Life 72.9 Hours

    Hours

    Fraction

    Remaining

    		 

    Hours

    Fraction

    Remaining

    0*

    1.00

    		 

    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

    0.71

    		 

    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

  • 12 CLINICAL PHARMACOLOGY

    12.1 Mechanism of Action

    Thallous Chloride Tl 201 with no carrier added accumulates in viable myocardium in a manner analogous to that of potassium.  Experiments in human volunteers using labeled microspheres have shown that the myocardial distribution of Thallous Chloride Tl 201 correlates well with regional perfusion.

    In clinical studies, Thallous Chloride Tl 201 images have been found to visualize areas of infarction as “cold” or nonlabeled regions which are 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 was administered in conjunction with an exercise stress test. Anatomic configurations may interfere with visualization of the right coronary artery.

    12.3 Pharmacokinetics

    After intravenous administration, Thallous Chloride Tl 201 clears rapidly from the blood with maximal concentration by 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. Thallous Chloride Tl 201 is excreted slowly and to an equal extent in both feces and urine.

    Five minutes after intravenous administration only 5 to 8 percent of injected activity remained in the blood. A biexponential disappearance curve was obtained, with 91.5 percent of the blood radioactivity disappearing with a half-time of about 5 minutes. The remainder had a half-time of about 40 hours.

    Approximately 4 to 8 percent 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 percent of the injected activity and the testicular content was 0.15 percent. Net thyroid activity was determined to be only 0.2 percent of the injected dose, and the activity disappeared in 24 hours. From anterior and posterior whole-body scans, it was determined that about 45 percent of the injected dose was in the large intestines and contiguous structures (liver, kidneys, abdominal musculature).

  • 13 NONCLINICAL TOXICOLOGY

    13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility

    No long-term animal studies have been performed to evaluate carcinogenic potential, mutagenic potential or whether this drug affects fertility in males or females.

  • 15 REFERENCES

    1Krahwinkel W, Herzog H, Feinendegen LE. Pharmacokinetics of
    thallium-201 in normal individuals after routine myocardial scintigraphy.
    J Nucl Med, 1988; 29, 1582–1586.

    2Thomas SR, Stabin MG, Castronovo FP. Radiation-absorbed dose from
    201Tl-thallous chloride. J Nucl Med, 2005; 46(3), 502-508.

    3Stabin MG, da Luz CQPL. New Decay Data for Internal and External Dose Assessment, Health Phys, 2002; 83(4), 471-475.

    4Data supplied by Oak Ridge Associated Universities, Radiopharmaceutical Internal Dose Information Center, Oak Ridge, TN, 1994.

  • 16 HOW SUPPLIED/STORAGE AND HANDLING

    16.1 How Supplied

    Thallous Chloride Tl 201 Injection is supplied in a sterile, non-pyrogenic solution for intravenous administration (Table 6). Each mL contains 37 MBq (1 mCi) Thallous Chloride Tl 201 at calibration time, 9 mg sodium chloride and 0.9 percent (v/v) benzyl alcohol. The pH is adjusted to between 4.5 to 7.0 with hydrochloric acid and/or sodium hydroxide solution. 

    Table 6. Thallous Chloride TI 201 Injection

    NDC

    Vial

    Volume

    Activity

    mL

    megabecquerels

    millicuries

    69945-120-28

    2.8 mL

    103.6

    2.8

    69945-120-56

    5.6 mL

    207.2

    5.6

    69945-120-63

    6.3 mL

    233.1

    6.3

    69945-120-99

    9.9 mL

    366.3

    9.9

    16.2 Handling

    The contents of the vial are radioactive. Adequate shielding and handling precautions must be maintained.

    16.3 Storage and Disposal

    Store this drug at controlled room temperature, 20° to 25°C (68° to 77°F).

    Storage and disposal of Thallous Chloride Tl 201 Injection should be controlled in a manner that is in compliance with the appropriate regulations of the government agency authorized to license the use of this radionuclide.

  • 17 PATIENT COUNSELING INFORMATION

    Advise patients to inform their physician or healthcare provider if they are pregnant or breast-feeding.

    Curium and the Curium logo are trademarks of a Curium company.
    ©2018 Curium US LLC. All Rights Reserved.

    Manufactured by:
    Curium US LLC
    Maryland Heights, MO 63043

    Made in USA

    A120I0
    Issued R12/2018

    CURIUM™

  • PRINCIPAL DISPLAY PANEL

    Thallous Chlloride TI 201 Injection
    DIAGNOSTIC Sterile, Non-Pyrogenic Solution
    For Intravenous Administration
    Store at Controlled Room Temperature 20º to 25ºC (68º to 77ºF) [see USP].

    Each milliliter contains 37 MBq (1 mCi) Thallous Chloride TI 201 (no carrier added) at date and time of calibration.  9 mg sodium chloride, and 0.9% (v/v) benzyl alcohol as a preservative.  Sodium hydroxide and/or hydrochloric acid are added for pH adjustment.  The pH is between 4.5 and 7.0.

    For information on dosage, administration and indications see package insert.

    Rx only

    WARNING:  Radioactive drugs must be handled only by qualified personnel in conformity with regulation of the U.S. Nuclear Regulatory Commission or state regulatory agencies where applicable.  Bottle containing drug should be kept in this container or within a heavier shield.

    CAUTION RADIOACTIVE MATERIAL

    Manufactured by:
    Curium US LLC
    Maryland Heights, MO 63043

    Made in USA

    CURIUM™

    A120C0

    R12/2018

    Display Panel A120CO
  • INGREDIENTS AND APPEARANCE
    THALLOUS CHLORIDE TL 201 
    thallous chloride, tl 201 injection, solution
    Product Information
    Product TypeHUMAN PRESCRIPTION DRUGItem Code (Source)NDC: 69945-120
    Route of AdministrationINTRAVENOUS
    Active Ingredient/Active Moiety
    Ingredient NameBasis of StrengthStrength
    THALLOUS CHLORIDE TL-201 (UNII: 3I8Y076A0E) (THALLOUS CATION TL-201 - UNII:4877X14G4C) THALLOUS CATION TL-2011 mCi  in 1 mL
    Inactive Ingredients
    Ingredient NameStrength
    SODIUM CHLORIDE (UNII: 451W47IQ8X)  
    BENZYL ALCOHOL (UNII: LKG8494WBH)  
    HYDROCHLORIC ACID (UNII: QTT17582CB)  
    SODIUM HYDROXIDE (UNII: 55X04QC32I)  
    Packaging
    #Item CodePackage DescriptionMarketing Start DateMarketing End Date
    1NDC: 69945-120-281 in 1 CAN11/04/2015
    12.8 mL in 1 VIAL; Type 0: Not a Combination Product
    2NDC: 69945-120-561 in 1 CAN11/04/2015
    25.6 mL in 1 VIAL; Type 0: Not a Combination Product
    3NDC: 69945-120-631 in 1 CAN11/04/2015
    36.3 mL in 1 VIAL; Type 0: Not a Combination Product
    4NDC: 69945-120-991 in 1 CAN11/04/2015
    49.9 mL in 1 VIAL; Type 0: Not a Combination Product
    Marketing Information
    Marketing CategoryApplication Number or Monograph CitationMarketing Start DateMarketing End Date
    NDANDA01815011/04/2015
    Labeler - Curium US LLC (079875617)
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