This site is intended for healthcare professionals
Abstract digital waveforms in blue and purple
  • Home
  • /
  • Drugs
  • /
  • A
  • /
  • Ammonia N 13
  • /
  • Ammonia N 13 AMMONIA N-13 37.5 mCi/mL THE FEINSTEIN INSTITUTES FOR MEDICAL RESEARCH
FDA Drug information

Ammonia N 13

Read time: 6 mins
Marketing start date: 06 Oct 2024

Summary of product characteristics


Adverse Reactions

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. To report SUSPECTED ADVERSE REACTIONS, contact The Feinstein Institutes for Medical Research at 516-562-1052 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch .

Contraindications

4 CONTRAINDICATIONS None None

Description

11 DESCRIPTION 11.1 Chemical Characteristics Ammonia N 13 Injection is a positron emitting radiopharmaceutical that is used for diagnostic purposes in conjunction with positron emission tomography (PET) imaging. The active ingredient, [ 13 N] ammonia, has the molecular formula of 13 NH 3 with a molecular weight of 16.02, and has the following chemical structure: Ammonia N 13 Injection is provided as a ready to use sterile, pyrogen-free, clear, and colorless solution. Each mL of the solution contains between 0.138 GBq to 1.387 GBq (3.75 mCi to 37.5 mCi) of [ 13 N] ammonia, at the end of synthesis (EOS) reference time, in 0.9% aqueous sodium chloride. The pH of the solution is between 4.5 to 7.5. The recommended dose of radioactivity (10-20 mCi) is associated with a theoretical mass dose of 0.05-0.1 picomoles (8.47-16.94 picograms) of ammonia. NH3 Structure 11.2 Physical Characteristics Nitrogen N 13 decays by emitting positron to Carbon C 13 (stable) and has a physical half-life of 9.96 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(β+) 100 1190 keV (Max.) Gamma(±)* 200 511 keV *Produced by positron annihilation The specific gamma ray constant (point source air kerma coefficient) for nitrogen N 13 is 5.9 R/hr/mCi (1.39 x 10 -6 Gy/hr/kBq) at 1 cm. The half-value layer (HVL) of lead (Pb) for 511 keV photons is 4 mm. 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 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 Coefficient of Attenuation 4 0.5 8 0.25 13 0.1 26 0.01 39 0.001 52 0.0001 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 0* 1.000 5 0.706 10 0.499 15 0.352 20 0.249 25 0.176 30 0.124 *Calibration time

Dosage And Administration

2 DOSAGE AND ADMINISTRATION Rest Imaging Study ( 2.1 ): • Aseptically withdraw Ammonia N 13 Injection from its container and administer 10-20 mCi (0.370 – 0.740 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 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 (0.370 – 0.740 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 (0.370 – 0.740 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 (0.370 – 0.740 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 0.013 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.

Indications And Usage

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.

Drug Interactions

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.

Clinical Pharmacology

12 CLINICAL PHARMACOLOGY 12.1 Mechanism of Action Ammonia N 13 Injection 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. 12.2 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. 12.3 Pharmacokinetics Following intravenous injection, Ammonia N 13 Injection is cleared from the blood with a biologic half-life of about 2.84 minutes (effective half-life of about 2.21 minutes). In the myocardium, its biologic half-life has been estimated to be less than 2 minutes (effective half-life less than 1.67 minutes). The mass dose of Ammonia N 13 Injection is very small as compared to the normal range of ammonia in the blood (0.72-3.30 mg) in a healthy adult man [see Description ( 11.1 )] . 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 have not been studied in renally impaired, hepatically impaired, or pediatric patients.

Effective Time

20191030

Version

20191030

Description Table

Table 2. Principal Radiation Emission Data for Nitrogen 13
Radiation/Emission % Per Disintegration Energy
Positron(β+) 100 1190 keV (Max.)
Gamma(±)* 200 511 keV

Dosage And Administration Table

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 0.013 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

Dosage Forms And Strengths

3 DOSAGE FORMS AND STRENGTHS Glass vial (25 mL) containing 0.138-1.387 GBq (3.75-37.5 mCi/mL) of Ammonia N 13 Injection in aqueous 0.9 % sodium chloride solution (approximately 8 mL volume) that is suitable for intravenous administration. Glass vial containing 0.138-1.387 GBq (3.75-37.5 mCi/mL) of Ammonia N 13 Injection in aqueous 0.9 % sodium chloride solution (approximately 8 mL volume).

Spl Product Data Elements

Ammonia N 13 NH3N13 AMMONIA N-13 AMMONIA N-13

Nonclinical Toxicology

13 NONCLINICAL TOXICOLOGY 13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility Long term animal studies have not been performed to evaluate the carcinogenic potential of Ammonia N 13 Injection. Genotoxicity assays and impairment of male and female fertility studies with Ammonia N 13 Injection have not been performed.

Application Number

NDA022119

Brand Name

Ammonia N 13

Generic Name

NH3N13

Product Ndc

13267-456

Product Type

HUMAN PRESCRIPTION DRUG

Route

INTRAVENOUS

Package Label Principal Display Panel

NH3 Vial Label NH3 Lead Pig Label

Spl Unclassified Section

Manufactured & Distributed by: The Feinstein Institutes for Medical Research Cyclotron/Radiochemistry Facility 350 Community Drive Manhasset, New York 11030

Information For Patients

17 PATIENT COUNSELING INFORMATION 17.1 Pre-study Hydration Instruct patients to drink plenty of water or other fluids (as tolerated) in the 4 hours before their PET study. 17.2 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. 17.3 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.

Clinical Studies

14 CLINICAL STUDIES In a descriptive, prospective, blinded image interpretation study 2 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).

References

15 REFERENCES 1 Annals of the ICRP. Publication 53. Radiation dose to patients from radiopharmaceuticals. New York: Pergamon Press, 1988. 2 Demer, L.L.K.L. Gould, R.A. Goldstein, R.L. Kirkeeide, N.A. Mullani, R.W. Smalling, A. Nishikawa, and M.E. Merhige. Assessment of coronary artery disease severity by PET: Comparison with quantitative arteriography in 193 patients. Circulation 1989; 79: 825-35.

Use In Specific Populations

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 )] .

How Supplied

16 HOW SUPPLIED/STORAGE AND HANDLING Ammonia N 13 Injection is packaged in 25 mL multiple dose glass vial containing between 1.11 GBq to 11.1 GBq (30 mCi to 300 mCi) of [ 13 N] ammonia, at the end of synthesis (EOS) reference time, in 0.9% 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 0.05-0.1 picomoles (8.47-16.94 picograms) of Ammonia. Storage Store at 25°C (77°F); excursions permitted to 15-30°C (59-86°F). Use the solution within 30 minutes of the End of Synthesis (EOS) calibration.

Learning Zones

The Learning Zones are an educational resource for healthcare professionals that provide medical information on the epidemiology, pathophysiology and burden of disease, as well as diagnostic techniques and treatment regimens.

Disclaimer

The drug Prescribing Information (PI), including indications, contra-indications, interactions, etc, has been developed using the U.S. Food & Drug Administration (FDA) as a source (www.fda.gov).

Medthority offers the whole library of PI documents from the FDA. Medthority will not be held liable for explicit or implicit errors, or missing data.

Drugs appearing in this section are approved by the FDA. For regions outside of the United States, this content is for informational purposes only and may not be aligned with local regulatory approvals or guidance.