Ammonia N 13 by NukeMed, Inc. dba SpectronRx AMMONIA N 13 injection
Ammonia N 13 by
Drug Labeling and Warnings
Ammonia N 13 by is a Prescription medication manufactured, distributed, or labeled by NukeMed, Inc. dba SpectronRx. Drug facts, warnings, and ingredients follow.
Drug Details [pdf]
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HIGHLIGHTS OF PRESCRIBING INFORMATION
HIGHLIGHTS OF PRESCRIBING INFORMATION
These highlights do not include all the information needed to use Ammonia N 13 Injection
safely and effectively. See full prescribing information for Ammonia N 13 Injection.
Ammonia N 13 Injection for intravenous use
Initial U.S. Approval: 2007INDICATIONS AND USAGE
INDICATIONS AND USAGE
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). (1)DOSAGE AND ADMINISTRATION
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)DOSAGE FORMS AND STRENGTHS
DOSAGE FORMS AND STRENGTHS
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)(3). (3)CONTRAINDICATIONS
CONTRAINDICATIONS
None(4) (4)WARNINGS AND PRECAUTIONS
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)ADVERSE REACTIONS
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
system(6).
To report SUSPECTED ADVERSE REACTIONS, contact Spectron mrc, LLC at 574-271-
2800 or FDA at 1-800-332-1088 or www.fda.gov/medwatch. (6) (6)USE IN SPECIFIC POPULATIONS
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).
See 17 for Patient Counseling Information
Revised: 01/2012 (7)DRUG INTERACTIONS
DRUG INTERACTIONS
The possibility of interactions of Ammonia N 13 Injection with other drugs taken by patients undergoing
PET imaging has not been studied. (8)Revised: 4/2015
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Table of Contents
FULL PRESCRIBING INFORMATION: CONTENTS*
Indications and Usage
Dosage and Administration
Dosage Forms and Strengths
Contraindications
Warnings and Precautions
Adverse Reactions
Use In Specific Populations
Drug Interactions
Description
Clinical Pharmacology
Nonclinical Toxicology
Clinical Studies
References
How Supplied
- * Sections or subsections omitted from the full prescribing information are not listed.
- Indications and Usage
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Dosage and Administration
2 DOSAGE AND ADMINISTRATION
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 Age (years)
Adult 15 10 5 1
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. - Dosage Forms and Strengths
- Contraindications
- Warnings and Precautions
- Adverse Reactions
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Use In Specific Populations
8 USE IN SPECIFIC POPULATIONS
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)]. - Drug Interactions
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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, [13N] ammonia,
has the molecular formula of 13NH3 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 37.5mCi) of [13N]
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 0.5-1.0 picomoles (8.47-16.94 picograms) of ammonia.
11.2 Physical Characteristics
Nitrogen N13 decays by emitting positron to Carbon C13 (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 N13 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 -
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 threecompartmental
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 halflife
of about 2.84 minutes (effective half-life of about 2.21 minutes). In the myocardium, its biologic halflife
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. -
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. -
Clinical Studies
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) -
References
15 REFERENCES
1Annals of the ICRP. Publication 53. Radiation dose to patients from radiopharmaceuticals. New York:
Pergamon Press, 1988.
2Demer, 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. -
How Supplied
16 HOW SUPPLIED
Ammonia N 13 Injection is packaged in a multiple dose glass vial (10, 25, 30, or 50 mL) containing
between 1.11 GBq to 11.1 GBq (30 mCi to 300 mCi) of [13N] 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 0.5-1.0
picomoles (8.47-16.94 picograms) of Ammonia.
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. - Package Label
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INGREDIENTS AND APPEARANCE
AMMONIA N 13
ammonia n 13 injectionProduct Information Product Type HUMAN PRESCRIPTION DRUG Item Code (Source) NDC: 13108-311 Route of Administration INTRAVENOUS Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength AMMONIA N-13 (UNII: 9OQO0E343Z) (AMMONIA N-13 - UNII:9OQO0E343Z) AMMONIA N-13 37.5 mCi in 1 mL Packaging # Item Code Package Description Marketing Start Date Marketing End Date 1 NDC: 13108-311-25 1 mL in 1 VIAL, GLASS; Type 0: Not a Combination Product 04/24/2015 Marketing Information Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date ANDA ANDA204455 04/24/2015 Labeler - Spectron mrc, LLC (131314853) Registrant - Spectron mrc, LLC (131314853) Establishment Name Address ID/FEI Business Operations Spectron mrc, LLC 131314853 positron emission tomography drug production(13108-311)
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