Xenon, Xe-133

ADVERSE REACTIONS Adverse reactions specifically attributable to Xenon Xe 133 Gas have not been reported.

CONTRAINDICATIONS None known.

DESCRIPTION Xenon Xe 133 Gas is for diagnostic inhalation use only. It is supplied in vials containing either 370 or 740 megabecquerels (10 or 20 millicuries) of Xenon Xe 133 Gas in 2 milliliters of carrier xenon and atmospheric air. Xenon Xe 133 Gas is chemically and physiologically similar to elemental xenon, a non-radioactive gas which is physiologically inert except for anesthetic properties at high doses. Xenon Xe 133 is produced by fission of Uranium U 235. At the time of calibration, it contains no more than 0.3% Xenon Xe 133m, no more than 1.5% Xenon Xe 131m, no more than 0.06% Krypton Kr 85 and no more than 0.01% Iodine I 131, with no less than 99.9% total radioactivity as radioxenon. Table 1 shows the effect of time on radionuclidic composition. Table 1. Radionuclidic Composition Percent of Total Radioactivity Days % Xe-133 % Xe-133m % Xe-131m % Kr-85 % I-131 -5 >98.3 <0.6 <1.0 <0.03 <0.01 0 Calibration Date >98.1 <0.3 <1.5 <0.06 <0.01 7 >97.2 <0.08 <2.5 <0.15 <0.02 14 Expiration Date >95.7 <0.02 <4.1 <0.37 <0.02

DOSAGE AND ADMINISTRATION Xenon Xe 133 Gas is administered by inhalation from a closed respirator system or spirometer. The final patient dose should be measured by a suitable radioactivity calibration system immediately prior to administration. The recommended activity range employed for inhalation by the average patient (70 kg) is: Pulmonary function including imaging: 74 to 1110 megabecquerels (2 to 30 millicuries) Cerebral blood flow: 370 to 1110 megabecquerels (10 to 30 millicuries) This may be administered as a bolus into the tubing near the patient's mouthpiece or mask after the completion of a tidal exhalation, or by rebreathing for a period of approximately 5 minutes of the Xenon Xe 133 gas in equilibrium with the air contained in the closed system at concentrations of the radionuclide that may vary from 37 to 222 megabecquerels (1.0 to 6.0 millicuries) per liter.

INDICATIONS AND USAGE Xenon Xe 133 Gas has been shown to be valuable for diagnostic inhalation studies for the evaluation of pulmonary function, for imaging the lungs and may also be applied to assessment of cerebral blood flow.

WARNINGS Xenon Xe 133 Gas delivery systems, i.e., respirators or spirometers, and associated tubing assemblies must be leakproof to avoid loss of radioactivity into the laboratory environs not specifically protected by exhaust systems. Xenon Xe 133 Gas adheres to some plastics and rubber and should not be allowed to stand in tubing or respirator containers. Loss of radioactivity due to such adherence may render the study nondiagnostic.

CLINICAL PHARMACOLOGY Xenon Xe 133 is a readily diffusible gas which is neither utilized nor produced by the body. It passes through cell membranes, freely exchanges between blood and tissue, and tends to concentrate more in body fat than in blood, plasma, water or protein solutions. In the concentrations recommended for diagnostic studies, it is physiologically inactive. Inhaled Xenon Xe 133 Gas will enter the alveolar wall and the pulmonary venous circulation via capillaries. Most of the Xenon Xe 133 Gas that enters the circulation from a single breath is returned to the lungs and exhaled after a single pass through the peripheral circulation.

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Xenon, Xe-133 Xenon XENON XE-133 XENON XE-133 AIR Xenon, Xe-133 Xenon XENON XE-133 XENON XE-133 AIR

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.

NDA018327

Xenon, Xe-133

Xenon

69945-097

HUMAN PRESCRIPTION DRUG

RESPIRATORY (INHALATION)

PRINCIPAL DISPLAY PANEL - 10 mCi XENON Xe 133 GAS 370 MBq (10 mCi)/vial CAUTION RADIOACTIVE MATERIAL Single Dose Container -Dispose in Accordance with Regulatory Requirements. For use with Xenotron™ I Xenon Gas Dispenser only. Rx only Curium US LLC A097V0 R03/2019 Label Label

PHYSICAL CHARACTERISTICS Xenon Xe 133 decays by beta and gamma emissions with a physical half-life of 5.245 days. Kocher, David C., "Radioactive Decay Data Tables," DOE/TIC-11026, 138 (1981). Photons that are useful for detection and imaging studies as well as the principal beta emission are listed in Table 2. Table 2. Principal Radiation Emission Data Radiation Mean % Per Disintegration Energy (keV) Beta-2 99.3 100.6 Avg. Gamma-2 36.5 81.0 K alpha x-rays 38.9 30.8 Avg. K beta x-rays 9.1 35.0 Avg.

Nursing Mothers It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when Xenon Xe 133 Gas is administered to a nursing woman.

Pediatric Use Safety and effectiveness in pediatric patients have not been established.

Pregnancy Category C Animal reproduction studies have not been conducted with Xenon Xe 133 Gas. It is also not known whether Xenon Xe 133 Gas can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. Xenon Xe 133 Gas should be given to a pregnant woman only if clearly needed. Ideally, all examinations that use radiopharmaceuticals, especially those elective in nature, of a woman of childbearing capability should be performed during the first few (approximately 10) days following the onset of menses.

HOW SUPPLIED Xenon Xe 133 Gas is available in 2 milliliter vials with color-coded labels in 370 megabecquerel (10 millicurie; Catalog No. 097) and 740 megabecquerel (20 millicurie; Catalog No. 098) sizes. Both sizes are available in packages of 1, 3 and 5 vials, each with individual lead shielding.

STORAGE Xenon Xe 133 Gas should be stored at controlled room temperature 20° to 25°C (68° to 77°F). [See USP Controlled Room Temperature.] The U.S. Nuclear Regulatory Commission has approved distribution of this radiopharmaceutical to persons licensed to use byproduct material listed in Sections 35.200 and to persons who hold an equivalent license issued by an Agreement State. Curium and the Curium logo are trademarks of a Curium company. ©2018 Curium US LLC. All Rights Reserved. Curium US LLC Maryland Heights, MO 63043 USA A097I0 R12/2018 CURIUM™

General Xenon Xe 133 Gas as well as other radioactive drugs, must be handled with care and appropriate safety measures should be used to minimize radiation exposure to clinical personnel. Also, care should be taken to minimize radiation exposure to the patients consistent with proper patient management. Exhaled Xenon Xe 133 Gas should be controlled in a manner that is in compliance with the appropriate regulations of the government agency authorized to license the use of radionuclides. Radiopharmaceuticals should be used only by physicians who are qualified by training and experience in the safe use and handling of radionuclides and whose experience and training have been approved by the appropriate government agency authorized to license the use of radionuclides.

PRECAUTIONS General Xenon Xe 133 Gas as well as other radioactive drugs, must be handled with care and appropriate safety measures should be used to minimize radiation exposure to clinical personnel. Also, care should be taken to minimize radiation exposure to the patients consistent with proper patient management. Exhaled Xenon Xe 133 Gas should be controlled in a manner that is in compliance with the appropriate regulations of the government agency authorized to license the use of radionuclides. Radiopharmaceuticals should be used only by physicians who are qualified by training and experience in the safe use and handling of radionuclides and whose experience and training have been approved by the appropriate government agency authorized to license the use of radionuclides. 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. Pregnancy Category C Animal reproduction studies have not been conducted with Xenon Xe 133 Gas. It is also not known whether Xenon Xe 133 Gas can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. Xenon Xe 133 Gas should be given to a pregnant woman only if clearly needed. Ideally, all examinations that use radiopharmaceuticals, especially those elective in nature, of a woman of childbearing capability should be performed during the first few (approximately 10) days following the onset of menses. Nursing Mothers It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when Xenon Xe 133 Gas is administered to a nursing woman. Pediatric Use Safety and effectiveness in pediatric patients have not been established.