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Radiopharmaceuticals that may potentially have unapproved copies of FDA-approved commercially available radiopharmaceuticals in the 10 | 61Package Inserts may be viewed at NamesApproved Indications in Adults (Pediatric use as noted)1Carbon-11 cholineMayo Clinic Indicated for PET imaging of patients with suspected prostate cancer recurrence based upon elevated blood prostate specific antigen (PSA) levels following initial therapy and non-informative bone scintigraphy, computerized tomography (CT) or magnetic resonance imaging (MRI) to help identify potential sites of prostate cancer recurrence for subsequent histologic confirmation2Carbon-14 urea Kimberly-ClarkPYtestDetection of gastric urease as an aid in the diagnosis of infection in the stomach3Fluorine-18 florbetabenPiramal ImagingNeuraceq Indicated for Positron Emission Tomography (PET) imaging of the brain to estimate amyloid neuritic plaque density in adult patients with cognitiveimpairment who are being evaluated for Alzheimer s disease (AD) or other causesof cognitive decline4Fluorine-18 florbetapirEli LillyAmyvid 5Fluorine-18 sodium fluoride1 Various PET bone imaging agent to delineate areas of altered osteogenesisNote: See page six for footnotesFDA-approved radiopharmaceuticalsThis is a current list of all FDA-approved radiopharmaceuticals. Nuclear medicine practitioners that receive radiopharmaceuticals that originate from sources other than the manufacturers listed in these tables may be using unapproved ManagementRadiopharmaceuticals that may potentially have unapproved copies of FDA-approved commercially available radiopharmaceuticals in the 10 | 62Package Inserts may be viewed at NamesApproved Indications in Adults (Pediatric use as noted)6Fluorine-18 fludeoxyglucose1 Various As a PET imaging agent to: Assess abnormal glucose metabolism in oncology Assess myocardial hibernation Identify regions of abnormal glucose metabolism associated with foci of epileptic seizures7Fluorine-18 flutemetamolGE HealthcareVizamylIndicated for Positron Emission Tomography (PET) imaging of the brain to estimate amyloid neuritic plaque density in adult patients with cognitive impairment who are being evaluated for Alzheimer s disease (AD) or other causes of cognitive decline8Gallium-67 citrateCovidien Useful to demonstrate the presence/extent of: Hodgkin s disease Lymphoma Bronchogenic carcinoma Aid in detecting some acute inflammatory lesionsLantheus Medical Imaging 9Indium-111 capromab pendetideJazz PharmaceuticalsProstaScint A diagnostic imaging agent in newly-diagnosed patients with biopsy-proven prostate cancer, thought to be clinically-localized after standard diagnostic evaluation ( chest x-ray, bone scan, CT scan, or MRI), who are at high-risk for pelvic lymph node metastases A diagnostic imaging agent in post-prostatectomy patients with a rising PSA and a negative or equivocal standard metastatic evaluation in whom there is a high clinical suspicion of occult metastatic disease10Indium-111 chlorideCovidien Indicated for radiolabeling: ProstaScint used for in vivo diagnostic imaging proceduresGE HealthcareIndiclor 11Indium-111 pentetate GE Healthcare For use in radionuclide cisternography12Indium-111 oxyquinolineGE Healthcare Indicated for radiolabeling autologous leukocytes which may be used as an adjunct in the detection of inflammatory processes to which leukocytes migrate, such as those associated with abscesses or other infection13Indium-111 pentetreotideCovidienOctreoscan An agent for the scintigraphic localization of primary and metastatic neuroendocrine tumors bearing somatostatin receptors14Iodine I-123 iobenguane GE HealthcareAdreView Indicated for use in the detection of primary or metastatic pheochromocytoma or neuroblastoma as an adjunct to other diagnostic for scintigraphic assessment of sympathetic innervation of the myocardium by measurement of the heart to mediastinum (H/M) ratio of radioactivity uptake in patients with New York Heart Association (NYHA) class II or class III heart failure and left ventricular ejection fraction (LVEF) 35%. Among these patients, it may be used to help identify patients with lower one and two year mortality risks, as indicated by an H/M ratio Limitations of Use: In patients with congestive heart failure, its utility has not been established for: selecting a therapeutic intervention or for monitoring the response to therapy; using the H/M ratio to identify a patient with a high risk for I-123 ioflupane2GE HealthcareDaTscan Indicated for striatal dopamine transporter visualization using SPECT brain imaging to assist in the evaluation of adult patients with suspected Parkinsonian syndromes (PS) in whom it may help differentiate essential tremor due to PS (idiopathic Parkinson s disease, multiple system atrophy and progressive supranuclear palsy)Note: See page six for footnotesRadiopharmaceuticals that may potentially have unapproved copies of FDA-approved commercially available radiopharmaceuticals in the 10 | 63Package Inserts may be viewed at NamesApproved Indications in Adults (Pediatric use as noted)16Iodine I-123 sodium iodide capsulesCardinal Health Indicated for use in the evaluation of thyroid: Function MorphologyCovidien 17Iodine I-125 human serum albumin IsoTex Diagnostics JeanatopeIndicated for use in the determination of: Total blood Plasma volume18Iodine I-125 iothalamateIsoTex Diagnostics Glofil-125Indicated for evaluation of glomerular filtration 19Iodine I-131 human serum albuminIsoTex Diagnostics MegatopeIndicated for use in determinations of: Total blood and plasma volumes Cardiac output Cardiac and pulmonary blood volumes and circulation times Protein turnover studies Heart and great vessel delineation Localization of the placenta Localization of cerebral neoplasms20Iodine I-131 sodium iodideCovidien Diagnostic: Performance of the radioactive iodide (RAI) uptake test to evaluate thyroid function Localizing metastases associated with thyroid malignancies Therapeutic: Treatment of hyperthyroidism Treatment of carcinoma of the thyroidDRAXIMAGEHICON 21Molybdenum Mo-99 generatorCovidienUltra-TechneKow DTEGeneration of Tc-99m sodium pertechnetate for administration or radiopharmaceutical preparationGE HealthcareDRYTEC Lantheus Medical ImagingTechnelite 22Nitrogen-13 ammonia1Various 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 disease23Radium-223 dichlorideBayer HealthCare Pharmaceuticals Indicated for the treatment of patients with castration-resistant prostate cancer, symptomatic bone metastases and no known visceral metastatic disease24Rubidium-82 chlorideBracco DiagnosticsCardiogen-82 PET myocardial perfusion agent that is useful in distinguishing normal from abnormal myocardium in patients with suspected myocardial infarction25Samarium-153 lexidronamLantheus Medical ImagingQuadramet Indicated for relief of pain in patients with confirmed osteoblastic metastatic bone lesions that enhance on radionuclide bone scanRadiopharmaceuticals that may potentially have unapproved copies of FDA-approved commercially available radiopharmaceuticals in the 10 | 64Package Inserts may be viewed at NamesApproved Indications in Adults (Pediatric use as noted)26Strontium-89 chlorideGE HealthcareMetastron Indicated for the relief of bone pain in patients with painful skeletal metastases that have been confirmed prior to therapy27Technetium-99m bicisateLantheus Medical ImagingNeurolite SPECT imaging as an adjunct to conventional CT or MRI imaging in the localization of stroke in patients in whom stroke has already been diagnosed28Technetium-99m disofenin PharmalucenceHepatolite Diagnosis of acute cholecystitis as well as to rule out the occurrence of acute cholecystitis in suspected patients with right upper quadrant pain, fever, jaundice, right upper quadrant tenderness and mass or rebound tenderness, but not limited to these signs and symptoms29Technetium-99m exametazine GE HealthcareCeretec As an adjunct in the detection of altered regional cerebral perfusion in stroke Leukocyte labeled scintigraphy as an adjunct in the localization of intra abdominal infection and inflammatory bowel disease30Technetium-99m macroaggregated albumin DRAXIMAGE An adjunct in the evaluation of pulmonary perfusion (adult and pediatric) Evaluation of peritoneo-venous (LaVeen) shunt patency31Technetium-99m mebrofeninBracco DiagnosticsCholetec As a hepatobiliary imaging agentPharmalucence 32Technetium-99m medronateBracco DiagnosticsMDP-Bracco As a bone imaging agent to delineate areas of altered osteogenesisDRAXIMAGE DRAXIMAGEMDP-25GE HealthcareMDP MultidosePharmalucence 33Technetium-99m mertiatideCovidienTechnescan MAG3 In patients > 30 days of age as a renal imaging agent for use in the diagnosis of: Congenital and acquired abnormalities Renal failure Urinary tract obstruction and calculi Diagnostic aid in providing: Renal function Split function Renal angiograms Renogram curves for whole kidney and renal cortex34Technetium-99m oxidronate CovidienTechnescan HDPAs a bone imaging agent to delineate areas of altered osteogenesis (adult and pediatric use)35Technetium-99m pentetate DRAXIMAGE Brain imaging Kidney imaging: - To assess renal perfusion - To estimate glomerular filtration rateRadiopharmaceuticals that may potentially have unapproved copies of FDA-approved commercially available radiopharmaceuticals in the 10 | 65Package Inserts may be viewed at NamesApproved Indications in Adults (Pediatric use as noted)36Technetium-99m pyrophosphate CovidienTechnescan PYP As a bone imaging agent to delineate areas of altered osteogenesis As a cardiac imaging agent used as an adjunct in the diagnosis of acute myocardial infarction As a blood pool imaging agent useful for: - Gated blood pool imaging - Detection of sites of gastrointestinal bleeding Pharmalucence 37Technetium-99m red blood cells CovidienUltraTag Tc99m-labeled red blood cells are used for: Blood pool imaging including cardiac first pass and gated equilibrium imaging Detection of sites of gastrointestinal bleeding38Technetium-99m sestamibi Cardinal Health Myocardial perfusion agent that is indicated for: Detecting coronary artery disease by localizing myocardial ischemia (reversible defects) and infarction (non-reversible defects) Evaluating myocardial function Developing information for use in patient management decisionsPlanar breast imaging as a second line diagnostic drug after mammography to assist in the evaluation of breast lesions in patients with an abnormal mammogram or a palpable breast massCovidien DRAXIMAGE Lantheus Medical ImagingCardiolite Pharmalucence 39Technetium-99m sodium pertechnetate Covidien Brain Imaging (including cerebral radionuclide angiography)* Thyroid Imaging* Salivary Gland Imaging Placenta Localization Blood Pool Imaging (including radionuclide angiography)* Urinary Bladder Imaging (direct isotopic cystography) for the detection of vesico-ureteral reflux* Nasolacrimal Drainage System Imaging (*adult and pediatric use)GE Healthcare Lantheus Medical Imaging 40Technetium-99m succimer GE Healthcare An aid in the scintigraphic evaluation of renal parenchymal disorders41Technetium-99m sulfur colloidPharmalucence Imaging areas of functioning retriculoendothelial cells in the liver, spleen and bone marrow* It is used orally for: - Esophageal transit studies* - Gastroesophageal reflux scintigraphy* - Detection of pulmonary aspiration of gastric contents* Aid in the evaluation of peritoneo-venous (LeVeen) shunt patency To assist in the localization of lymph nodes draining a primary tumor in patients with breast cancer or malignant melanoma when used with a hand-held gamma counter(*adult and pediatric use)42Technetium-99mtetrofosminGE HealthcareMyoview Myocardial perfusion agent that is indicated for: Detecting coronary artery disease by localizing myocardial ischemia (reversible defects) and infarction (non-reversible defects) The assessment of left ventricular function (left ventricular ejection fraction and wall motion) of 66Rev. 10 | 2014 Cardinal Health. All rights reserved. Cardinal Health, the Cardinal Health LOGO, and ESSENTIAL TO CARE are trademarks or registered trademarks of Cardinal Health. All other marks are the property of their respective owners. Lit. No. 1NPS14-24612 (11/2014) Inserts may be viewed at to promulgation of 21 Part 212, Current Good Manufacturing Practices (cGMP) for PET Radiopharmaceuticals, firms manufacturing and distributing this drug are required to submit either a NDA or an ANDA by June 12, 2012 and manufacture following cGMP Part 212 regulations as of December 11, 2011 for its continued distribution and is a Schedule II controlled substance under the Controlled Substances Act. A DEA license is required for handling or administering this controlled reader of this document is cautioned that Cardinal Health makes no representation, guarantee, or warranty, express or implied as to the accuracy and appropriateness of the information contained in this document, and will bear no responsibility or liability for the results or consequences of its use. The information provided is for educational purposes Health 7000 Cardinal Place Dublin, Ohio 43017RadiopharmaceuticalManufacturerTrad e NamesApproved Indications in Adults (Pediatric use as noted)43Technetium-99m tilmanoceptNavidea Biopharmaceuticals, Inc. Lymphoseek Indicated with or without scintigraphic imaging for: Lymphatic mapping using a handheld gamma counter to locate lymph nodes draining a primary tumor site in patients with solid tumors for which this procedure is a component of intraoperative management. Guiding sentinel lymph node biopsy using a handheld gamma counter in patients with clinically node negative squamous cell carcinoma of the oral cavity, breast cancer or chlorideCovidien Useful in myocardial perfusion imaging for the diagnosis and localization of myocardial infarction As an adjunct in the diagnosis of ischemic heart disease (atherosclerotic coronary artery disease) Localization of sites of parathyroid hyperactivity in patients with elevated serum calcium and parathyroid hormone levelsGE Healthcare Lantheus Medical Imaging 45Xenon-133 gasLantheus Medical Imaging The evaluation of pulmonary function and for imaging the lungs Assessment of cerebral flow46Yttrium-90 chlorideMDS Nordion Indicated for radiolabeling: Zevalin used for radioimmunotherapy proceduresEckert & Ziegler Nuclitec 47Yttrium-90 ibritumomab tiuxetanSpectrum PharmaceuticalsZevalin Indicated for the: Treatment of relapsed or refractory, low-grade or follicular B-cell non-Hodgkin s lymphoma (NHL) Treatment of previously untreated follicular NHL in patients who achieve a partial or complete response to first-line chemotherapyHIGHLIGHTS OF PRESCRIBING INFORMATION These highlights do not include all the information needed to use Ammonia N-13 Injection, USP safely and effectively. See full prescribing information for Ammonia N-13 Injection, USP. Ammonia N-13 Injection, USP for intravenous use Initial Approval: 2007 ----------------------------INDICATIONS AND USAGE--------------------------- Ammonia N-13 Injection, USP 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). ----------------------DOSAGE AND ADMINISTRATION----------------------- Rest Imaging Study ( ): Aseptically withdraw Ammonia N-13 Injection, USP from its container and administer 10-20 mCi ( 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 ( ): If a rest imaging study is performed, begin the stress imaging study 40 minutes or more after the first Ammonia N-13 Injection, USP to allow sufficient isotope decay. Administer a pharmacologic stress-inducing drug in accordance with its labeling. Aseptically withdraw Ammonia N-13 Injection, USP from its container and administer 10-20 mCi ( GBq) of Ammonia N-13 Injection, USP 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, USP and acquire images for a total of 10-20 minutes. Patient Preparation ( ): 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. ---------------------DOSAGE FORMS AND STRENGTHS---------------------- Glass vial containing GBq ( mCi/mL) of Ammonia N-13 Injection, USP in aqueous % sodium chloride solution (approximately 8 mL volume) (3). -------------------------------CONTRAIND ICATIONS------------------------------ None (4) -----------------------WARNINGS AND PRECAUTIONS------------------------ Ammonia N-13 Injection, USP 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). ------------------------------ADVERSE REACTIONS------------------------------- No adverse reactions have been reported for Ammonia N-13 Injection, USP 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 Cardinal Health at 1-800-539-1503 or FDA at 1-800-FDA-1088 or -----------------------USE IN SPECIFIC POPULATIONS------------------------ It is not known whether this drug is excreted in human milk. Alternatives to breastfeeding ( 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, USP ( ). The safety and effectiveness of Ammonia N-13 Injection, USP has been established in pediatric patients ( ). See 17 for PATIENT COUNSELING INFORMATION Revised: 06/2013FULL PRESCRIBING INFORMATION: CONTENTS* 1 INDICATIONS AND USAGE 2 DOSAGE AND ADMINISTRATION Rest Imaging Study Stress Imaging Study Patient Preparation Radiation Dosimetry Drug Handling 3 DOSAGE FORMS AND STRENGTHS 4 CONTRAINDICATIONS 5 WARNINGS AND PRECAUTIONS Radiation Risks 6 ADVERSE REACTIONS 7 DRUG INTERACTIONS 8 USE IN SPECIFIC POPULATIONS Pregnancy Nursing Mothers Pediatric Use 11 DESCR IP TION Chemical Characteristics Physical Characteristics 12 CLINICAL PHARM ACOLOGY Mechanism of Action Pharmacodynamics Pharmacokinetics 13 NONCLINICAL TOXICOLOGY Carcinogenesis, Mutagenesis, Impairment of Fertility 14 CLINICAL STUDIES 15 REFERENCES 16 HOW SUPPLIED/STORAGE AND HANDLING 17 PATIENT COUNSELING INFORMATION Pre-study Hydration Post-study Voiding Post-study Breastfeeding Avoidance *Sections or subsections omitted from the full prescribing information are not listedFULL PRESCRIBING INFORMATION 1 INDICATIONS AND USAGE Ammonia N-13 Injection, USP 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. 2 DOSAGE AND ADMINISTRATION Rest Imaging Study Aseptically withdraw Ammonia N-13 Injection, USP from its container and administer 10-20 mCi ( 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 If a rest imaging study is performed, begin the stress imaging study 40 minutes or more after the first Ammonia N-13 Injection, USP to allow sufficient isotope decay. Administer a pharmacologic stress-inducing drug in accordance with its labeling. Aseptically withdraw Ammonia N-13 Injection, USP from its container and administer 10-20 mCi ( GBq) of Ammonia N-13 Injection, USP 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, USP and acquire images for a total of 10-20 minutes. 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. 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 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 Bladder wall Bone surfaces Brain Breast Stomach wall Small intestine 00013 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 *ULI **LLI Heart Kidneys Liver Lungs Ovaries Pancreas Red marrow Spleen Testes Thyroid Uterus Other tissues * Upper large intestine; ** Lower large intestine Drug Handling Inspect Ammonia N-13 Injection, USP visually for particulate matter and discoloration before administration, whenever solution and container permit. Do not administer Ammonia N-13 Injection, USP 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, USP. Use aseptic technique to maintain sterility during all operations involved in the manipulation and administration of Ammonia N-13 Injection, USP. 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, USP, assay the dose in a properly calibrated dose calibrator. 3 DOSAGE FORMS AND STRENGTHS Glass vial (10 mL) containing GBq ( mCi/mL) of Ammonia N-13 Injection, USP in aqueous % sodium chloride solution (approximately 8 mL volume) that is suitable for intravenous administration. 4 CONTRAINDICATIONS None 5 WARNINGS AND PRECAUTIONS Radiation Risks Ammonia N-13 Injection, USP 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 ( )]. 6 ADVERSE REACTIONS No adverse reactions have been reported for Ammonia N-13 Injection, USP 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. 7 DRUG INTERACTIONS The possibility of interactions of Ammonia N-13 Injection, USP with other drugs taken by patients undergoing PET imaging has not been studied. 8 USE IN SPECIFIC POPULATIONS Pregnancy Pregnancy Category C Animal reproduction studies have not been conducted with Ammonia N-13 Injection, USP. It is also not known whether Ammonia N-13 Injection, USP can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. Ammonia N-13 Injection, USP should be given to a pregnant woman only if clearly needed. 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, USP, use alternative infant nutrition sources ( 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. Pediatric Use The safety and effectiveness of Ammonia N-13 Injection, USP 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 ( )]. 11 DESCRIPTION Chemical Characteristics Ammonia N-13 Injection, USP is a positron emitting radiopharmaceutical that is used for diagnostic purposes in conjunction with positron emission tomography (PET) imaging. The active ingredient, [13N] ammonia, has the molecular formula of 13NH3 with a molecular weight of , and has the following chemical structure: Ammonia N-13 Injection, USP is provided as a ready to use sterile, pyrogen-free, clear and colorless solution. Each mL of the solution contains between GBq to GBq ( mCi to mCi) of [13N] ammonia, at the end of synthesis (EOS) reference time, in aqueous sodium chloride. The pH of the solution is between to The recommended dose of radioactivity (10-20 mCi) is associated with a theoretical mass dose of picomoles of ammonia. Physical Characteristics Nitrogen N-13 decays by emitting positron to Carbon C-13 (stable) and has a physical half-life of minutes. The principal photons useful for imaging are the dual 511 keV gamma photons that are produced and emitted simultaneously in opposite direction when the positron interacts with an electron (Table 2). Table 2: Principal Radiation Emission Data for Nitrogen 13 Radiation/Emission % Per Disintegration Energy Positron( +) 100 1190 keV (Max.) Gamma( )a 200 keV a) Produced by positron annihilation. The specific gamma ray constant (point source air kerma coefficient) for nitrogen N-13 is R/hr/mCi ( x 10-6 Gy/hr/kBq) at 1 cm. The half-value layer (HVL) of lead (Pb) for 511 keV photons is 4 mm, or mm tungsten (W) alloy. Selected coefficients of attenuation are listed in Table 3 as a function of lead shield thickness. For example, the use of 39 mm thickness of lead or 28 mm of tungsten alloy will attenuate the external radiation by a factor of about 1000. Table 3: Radiation Attenuation of 511 keV Photons by Lead (Pb) Shielding Shield Thickness (Pb) mm Shield Thickness ( W) All oy mm Coefficient of Attenuation 0 0 4 8 13 26 39 Table 4 lists fractions remaining at selected time intervals from the calibration time. This information may be used to correct for physical decay of the radionuclide. Table 4: Physical Decay Chart for Nitrogen N-13 Minutes Fraction Remaining 0a 5 10 15 20 25 30 60 a) calibration time 12 CLINICAL PHARMACOLOGY Mechanism of Action Ammonia N-13 Injection, USP is a radiolabeled analog of ammonia that is distributed to all organs of the body after intravenous administration. It is extracted from the blood in the coronary capillaries into the myocardial cells where it is metabolized to glutamine N-13 and retained in the cells. The presence of ammonia N-13 and glutamine N-13 in the myocardium allows for PET imaging of the myocardium. Pharmacodynamics Following intravenous injection, ammonia N-13 enters the myocardium through the coronary arteries. The PET technique measures myocardial blood flow based on the assumption of a three-compartmental disposition of intravenous ammonia N-13 in the myocardium. In this model, the value of the rate constant, which represents the delivery of blood to myocardium, and the fraction of ammonia N-13 extracted into the myocardial cells, is a measure of myocardial blood flow. Optimal PET imaging of the myocardium is generally achieved between 10 to 20 minutes after administration. Pharmacokinetics Following intravenous injection, Ammonia N-13 Injection, USP is cleared from the blood with a biologic half-life of about minutes (effective half-life of about minutes). In the myocardium, its biologic half-life has been estimated to be less than 2 minutes (effective half-life less than minutes). The mass dose of Ammonia N-13 Injection, USP is very small as compared to the normal range of ammonia in the blood ( mg) in a healthy adult man [see Description ( )]. Plasma protein binding of ammonia N-13 or its N-13 metabolites has not been studied. Ammonia N-13 undergoes a five-enzyme step metabolism in the liver to yield urea N-13 (the main circulating metabolite). It is also metabolized to glutamine N-13 (the main metabolite in tissues) by glutamine synthesis in the skeletal muscles, liver, brain, myocardium, and other organs. Other metabolites of ammonia N-13 include small amounts of N-13 amino acid anions (acidic amino acids) in the forms of glutamate N-13 or aspartate N-13. Ammonia N-13 is eliminated from the body by urinary excretion mainly as urea N-13. The pharmacokinetics of Ammonia N-13 Injection, USP have not been studied in renally impaired, hepatically impaired, or pediatric patients. 13 NONCLINICAL TOXICOLOGY Carcinogenesis, Mutagenesis, Impairment of Fertility Long term animal studies have not been performed to evaluate the carcinogenic potential of Ammonia N-13 Injection, USP. Genotoxicity assays and impairment of male and female fertility studies with Ammonia N-13 Injection, USP have not been performed. 14 CLINICAL STUDIES In a descriptive, prospective, blinded image interpretation study2 of adult patients with known or suspected coronary artery disease, myocardial perfusion deficits in stress and rest PET images obtained with Ammonia N-13 (N=111) or Rubidium 82 (N=82) were compared to changes in stenosis flow reserve (SFR) as determined by coronary angiography. The principal outcome of the study was the evaluation of PET defect severity relative to SFR. PET perfusion defects at rest and stress for seven cardiac regions (anterior, apical, anteroseptal, posteroseptal, anterolateral, posterolateral, and inferior walls) were graded on a 0 to 5 scale defined as normal (0), possible (1), probable (2), mild (3), moderate (4), and severe (5) defects. Coronary angiograms were used to measure absolute and relative stenosis dimensions and to calculate stenosis flow reserve defined as the maximum value of flow at maximum coronary vasodilatation relative to rest flow under standardized hemodynamic conditions. SFR scores ranged from 0 (total occlusion) to 5 (normal). With increasing impairment of flow reserve, the subjective PET defect severity increased. A PET defect score of 2 or higher was positively correlated with flow reserve impairment (SFR<3). 15 REFERENCES 1. Annals of the ICRP. Publication 53. Radiation dose to patients from radiopharmaceuticals. New York: Pergamon Press, 1988. 2. Demer, , , , , Smalling, , and Assessment of coronary artery disease severity by PET: Comparison with quantitative arteriography in 193 patients. Circulation 1989; 79: 825-35. 16 HOW SUPPLIED/STORAGE AND HANDLING Ammonia N-13 Injection, USP is packaged in 10 mL multiple dose glass vial containing between GBq (30 300 mCi/mL) of [13N] ammonia, at the end of synthesis (EOS) reference time, in sodium chloride injection solution in approximately 8 mL volume. The recommended dose of radioactivity (10-20 mCi) is associated with a theoretical mass dose of picomoles of Ammonia. NDC 65857-200-10 Storage Store at 25 C (77 F); excursions permitted to 15-30 C (59-86 F). Use the solution within 60 minutes of the End of Synthesis (EOS) calibration. 17 PATIENT COUNSELING INFORMATION Pre-study Hydration Instruct patients to drink plenty of water or other fluids (as tolerated) in the 4 hours before their PET study. Post-study Voiding Instruct patients to void after completion of each image acquisition session and as often as possible for one hour after the PET scan ends. Post-study Breastfeeding Avoidance Instruct nursing patients to substitute stored breast milk or infant formula for breast milk for 2 hours after administration of Ammonia N-13 Injection, USP. Manufactured by: Cardinal Health 414, LLC 7000 Cardinal Place Dublin, OH 43017 Distributed by: Cardinal Health 414, LLC 7000 Cardinal Place Dublin, OH 43017 Revised: 06/2013

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