Ammonia N 13

1 INDICATIONS AND USAGE Ammonia N 13 Injection is indicated for diagnostic Positron Emission Tomography (PET) imaging of the myocardium under rest or pharmacologic stress conditions to evaluate myocardial perfusion in patients with suspected or existing coronary artery disease. Ammonia N 13 Injection is a radioactive diagnostic agent for Positron Emission Tomography (PET) indicated for diagnostic PET imaging of the myocardium under rest or pharmacologic stress conditions to evaluate myocardial perfusion in patients with suspected or existing coronary artery disease ( 1 ).

2 DOSAGE AND ADMINISTRATION Rest Imaging Study ( 2.1 ): Aseptically withdraw Ammonia N 13 Injection from its container and administer 10-20 mCi (0.368 – 0.736 GBq) as a bolus through a catheter inserted into a large peripheral vein. Start imaging 3 minutes after the injection and acquire images for a total of 10-20 minutes. Stress Imaging Study ( 2.2 ): If a rest imaging study is performed, begin the stress imaging study 40 minutes or more after the first Ammonia N13 injection to allow sufficient isotope decay. Administer a pharmacologic stress-inducing drug in accordance with its labeling. Aseptically withdraw Ammonia N 13 Injection from its container and administer 10-20 mCi (0.368 – 0.736 GBq) of Ammonia N 13 Injection as a bolus at 8 minutes after the administration of the pharmacologic stress-inducing drug. Start imaging 3 minutes after the Ammonia N 13 Injection and acquire images for a total of 10-20 minutes. Patient Preparation ( 2.3 ): To increase renal clearance of radioactivity and to minimize radiation dose to the bladder, hydrate the patient before the procedure and encourage voiding as soon as each image acquisition is completed and as often as possible thereafter for at least one hour. 2.1 Rest Imaging Study Aseptically withdraw Ammonia N 13 Injection from its container and administer 10-20 mCi (0.368 – 0.736 GBq) as a bolus through a catheter inserted into a large peripheral vein. Start imaging 3 minutes after the injection and acquire images for a total of 10-20 minutes. 2.2 Stress Imaging Study If a rest imaging study is performed, begin the stress imaging study 40 minutes or more after the first Ammonia N 13 injection to allow sufficient isotope decay. Administer a pharmacologic stress-inducing drug in accordance with its labeling. Aseptically withdraw Ammonia N 13 Injection from its container and administer 10-20 mCi (0.368 – 0.736 GBq) of Ammonia N 13 Injection as a bolus at 8 minutes after the administration of the pharmacologic stress-inducing drug. Start imaging 3 minutes after the Ammonia N 13 Injection and acquire images for a total of 10-20 minutes. 2.3 Patient Preparation To increase renal clearance of radioactivity and to minimize radiation dose to the bladder, ensure that the patient is well hydrated before the procedure and encourage voiding as soon as a study is completed and as often as possible thereafter for at least one hour. 2.4 Radiation Dosimetry The converted radiation absorbed doses in rem/mCi are shown in Table 1. These estimates are calculated from the Task Group of Committee 2 of the International Commission on Radiation Protection. 1 Table 1: N 13 Absorbed Radiation Dose Per Unit Activity (rem/mCi) for Adults and Pediatric Groups. Organ Adult 15 - year old 10 - year old 5 - year old 1 - year old Adrenals 0.0085 0.0096 0.016 0.025 0.048 Bladder wall 0.030 0.037 0.056 0.089 0.17 Bone surfaces 0.0059 0.0070 0.011 0.019 0.037 Brain 0.016 0.016 0.017 0.019 0.027 Breast 0.0067 0.0067 0.010 0.017 0.033 Stomach wall 0.0063 0.0078 0.012 0.019 0.037 Small intestine 0.0067 0.0081 00013 0.021 0.041 *ULI 0.0067 0.0078 0.013 0.021 0.037 **LLI 0.0070 0.0078 0.013 0.020 0.037 Heart 0.0078 0.0096 0.015 0.023 0.041 Kidneys 0.017 0.021 0.031 0.048 0.089 Liver 0.015 0.018 0.029 0.044 0.085 Lungs 0.0093 0.011 0.018 0.029 0.056 Ovaries 0.0063 0.0085 0.014 0.021 0.041 Pancreas 0.0070 0.0085 0.014 0.021 0.041 Red marrow 0.0063 0.0078 0.012 0.020 0.037 Spleen 0.0093 0.011 0.019 0.030 0.056 Testes 0.0067 0.0070 0.011 0.018 0.035 Thyroid 0.0063 0.0081 0.013 0.021 0.041 Uterus 0.0070 0.0089 0.014 0.023 0.041 Other tissues 0.0059 0.0070 0.011 0.018 0.035 *Upper large intestine, **Lower large intestine 2.5 Drug Handling Inspect Ammonia N 13 Injection visually for particulate matter and discoloration before administration, whenever solution and container permit. Do not administer Ammonia N 13 Injection containing particulate matter or discoloration; dispose of these unacceptable or unused preparations in a safe manner, in compliance with applicable regulations. Wear waterproof gloves and effective shielding when handling Ammonia N 13 Injection. Use aseptic technique to maintain sterility during all operations involved in the manipulation and administration of Ammonia N 13 Injection. The contents of each vial are sterile and non-pyrogenic. Use appropriate safety measures, including shielding, consistent with proper patient management to avoid unnecessary radiation exposure to the patient, occupational workers, clinical personnel, and other persons. Radiopharmaceuticals should be used by or under the control of physicians 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. Before administration of Ammonia N 13 Injection, assay the dose in a properly calibrated dose calibrator. 2.1 Rest Imaging Study Aseptically withdraw Ammonia N 13 Injection from its container and administer 10-20 mCi (0.368 – 0.736 GBq) as a bolus through a catheter inserted into a large peripheral vein. Start imaging 3 minutes after the injection and acquire images for a total of 10-20 minutes. 2.2 Stress Imaging Study If a rest imaging study is performed, begin the stress imaging study 40 minutes or more after the first Ammonia N 13 injection to allow sufficient isotope decay. Administer a pharmacologic stress-inducing drug in accordance with its labeling. Aseptically withdraw Ammonia N 13 Injection from its container and administer 10-20 mCi (0.368 – 0.736 GBq) of Ammonia N 13 Injection as a bolus at 8 minutes after the administration of the pharmacologic stress-inducing drug. Start imaging 3 minutes after the Ammonia N 13 Injection and acquire images for a total of 10-20 minutes. 2.3 Patient Preparation To increase renal clearance of radioactivity and to minimize radiation dose to the bladder, ensure that the patient is well hydrated before the procedure and encourage voiding as soon as a study is completed and as often as possible thereafter for at least one hour. 2.4 Radiation Dosimetry The converted radiation absorbed doses in rem/mCi are shown in Table 1. These estimates are calculated from the Task Group of Committee 2 of the International Commission on Radiation Protection. 1 Table 1: N 13 Absorbed Radiation Dose Per Unit Activity (rem/mCi) for Adults and Pediatric Groups. Organ Adult 15 - year old 10 - year old 5 - year old 1 - year old Adrenals 0.0085 0.0096 0.016 0.025 0.048 Bladder wall 0.030 0.037 0.056 0.089 0.17 Bone surfaces 0.0059 0.0070 0.011 0.019 0.037 Brain 0.016 0.016 0.017 0.019 0.027 Breast 0.0067 0.0067 0.010 0.017 0.033 Stomach wall 0.0063 0.0078 0.012 0.019 0.037 Small intestine 0.0067 0.0081 00013 0.021 0.041 *ULI 0.0067 0.0078 0.013 0.021 0.037 **LLI 0.0070 0.0078 0.013 0.020 0.037 Heart 0.0078 0.0096 0.015 0.023 0.041 Kidneys 0.017 0.021 0.031 0.048 0.089 Liver 0.015 0.018 0.029 0.044 0.085 Lungs 0.0093 0.011 0.018 0.029 0.056 Ovaries 0.0063 0.0085 0.014 0.021 0.041 Pancreas 0.0070 0.0085 0.014 0.021 0.041 Red marrow 0.0063 0.0078 0.012 0.020 0.037 Spleen 0.0093 0.011 0.019 0.030 0.056 Testes 0.0067 0.0070 0.011 0.018 0.035 Thyroid 0.0063 0.0081 0.013 0.021 0.041 Uterus 0.0070 0.0089 0.014 0.023 0.041 Other tissues 0.0059 0.0070 0.011 0.018 0.035 *Upper large intestine, **Lower large intestine 2.5 Drug Handling Inspect Ammonia N 13 Injection visually for particulate matter and discoloration before administration, whenever solution and container permit. Do not administer Ammonia N 13 Injection containing particulate matter or discoloration; dispose of these unacceptable or unused preparations in a safe manner, in compliance with applicable regulations. Wear waterproof gloves and effective shielding when handling Ammonia N 13 Injection. Use aseptic technique to maintain sterility during all operations involved in the manipulation and administration of Ammonia N 13 Injection. The contents of each vial are sterile and non-pyrogenic. Use appropriate safety measures, including shielding, consistent with proper patient management to avoid unnecessary radiation exposure to the patient, occupational workers, clinical personnel, and other persons. Radiopharmaceuticals should be used by or under the control of physicians 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. Before administration of Ammonia N 13 Injection, assay the dose in a properly calibrated dose calibrator.

4 CONTRAINDICATIONS None None ( 4 )

5 WARNINGS AND PRECAUTIONS Ammonia N 13 Injection may increase the risk of cancer. Use the smallest dose necessary for imaging and ensure safe handling to protect the patient and health care worker ( 5 ). 5.1 Radiation Risks Ammonia N 13 Injection may increase the risk of cancer. Use the smallest dose necessary for imaging and ensure safe handling to protect the patient and health care worker [see Dosage and Administration (2.4)] . 5.1 Radiation Risks Ammonia N 13 Injection may increase the risk of cancer. Use the smallest dose necessary for imaging and ensure safe handling to protect the patient and health care worker [see Dosage and Administration (2.4)] .

7 DRUG INTERACTIONS The possibility of interactions of Ammonia N 13 Injection with other drugs taken by patients undergoing PET imaging has not been studied.

6 ADVERSE REACTIONS No adverse reactions have been reported for Ammonia N 13 Injection based on a review of the published literature, publicly available reference sources, and adverse drug reaction reporting systems. However, the completeness of these sources is not known. No adverse reactions have been reported for Ammonia N 13 Injection based on a review of the published literature, publicly available reference sources, and adverse drug reaction reporting system ( 6). To report SUSPECTED ADVERSE REACTIONS, contact University of Wisconsin Radiopharmaceutical Production Facility at (608) 263-0359 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

8 USE IN SPECIFIC POPULATIONS It is not known whether this drug is excreted in human milk. Alternatives to breastfeeding (e.g. using stored breast milk or infant formula) should be used for 2 hours (>10 half-lives of radioactive decay for N 13 isotope) after administration of Ammonia N 13 Injection ( 8.3 ). The safety and effectiveness of Ammonia N 13 Injection has been established in pediatric patients ( 8.4 ). 8.1 Pregnancy Pregnancy Category C Animal reproduction studies have not been conducted with Ammonia N 13 Injection. It is also not known whether Ammonia N 13 Injection can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. Ammonia N 13 Injection should be given to a pregnant woman only if clearly needed. 8.3 Nursing Mothers It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk and because of the potential for radiation exposure to nursing infants from Ammonia N 13 Injection, use alternative infant nutrition sources (e.g. stored breast milk or infant formula) for 2 hours (>10 half-lives of radioactive decay for N 13 isotope) after administration of the drug or avoid use of the drug, taking into account the importance of the drug to the mother. 8.4 Pediatric Use The safety and effectiveness of Ammonia N 13 Injection has been established in pediatric patients based on known metabolism of ammonia, radiation dosimetry in the pediatric population, and clinical studies in adults [see Dosage and Administration (2.4)]. 8.1 Pregnancy Pregnancy Category C Animal reproduction studies have not been conducted with Ammonia N 13 Injection. It is also not known whether Ammonia N 13 Injection can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. Ammonia N 13 Injection should be given to a pregnant woman only if clearly needed. 8.3 Nursing Mothers It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk and because of the potential for radiation exposure to nursing infants from Ammonia N 13 Injection, use alternative infant nutrition sources (e.g. stored breast milk or infant formula) for 2 hours (>10 half-lives of radioactive decay for N 13 isotope) after administration of the drug or avoid use of the drug, taking into account the importance of the drug to the mother. 8.4 Pediatric Use The safety and effectiveness of Ammonia N 13 Injection has been established in pediatric patients based on known metabolism of ammonia, radiation dosimetry in the pediatric population, and clinical studies in adults [see Dosage and Administration (2.4)].