SODIUM FLUORIDE F 18- sodium fluoride f-18 injection
Essential Isotopes LLC
HIGHLIGHTS OF PRESCRIBING INFORMATION
These highlights do not include all the information needed to use Sodium Fluoride F 18 Injection USP safely and effectively. See full prescribing information for Sodium Fluoride F 18 Injection USP.
SODIUM FLUORIDE F 18 INJECTION USP
For Intravenous Use
Initial U.S. Approval: 1/2011
INDICATIONS AND USAGE
Sodium Fluoride F 18 Injection USP is a radioactive diagnostic agent for positron emission tomography (PET) indicated for imaging of bone to define areas of altered osteogenic activity (1).
DOSAGE AND ADMINISTRATION
DOSAGE FORMS AND STRENGTHS
Multiple-dose vial containing 370–7,400 MBq/mL (10–200 mCi/mL) at EOS reference time of no-carrier-added sodium fluoride F 18 in aqueous 0.9% sodium chloride solution (3). Sodium Fluoride F 18 Injection USP is a clear, colorless, sterile, pyrogen-free and preservative-free solution for intravenous administration.
WARNINGS AND PRECAUTIONS
No adverse reactions have been reported for Sodium Fluoride F 18 Injection USP based on a review of the published literature, publicly available reference sources, and adverse drug reaction reporting systems (6).
To report SUSPECTED ADVERSE REACTIONS, contact Essential Isotopes LLC at 1-573-882-0245 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
USE IN SPECIFIC POPULATIONS
See 17 for PATIENT COUNSELING INFORMATION.
FULL PRESCRIBING INFORMATION: CONTENTS*
Sodium Fluoride F 18 Injection USP is indicated for diagnostic positron emission tomography (PET) imaging of bone to define areas of altered osteogenic activity.
In reported clinical experience in approximately 100 children, weight based doses (2.1 MBq/kg) ranging from 19 MBq– 148 MBq (0.5 mCi - 4 mCi) were used.
The age/weight-based estimated absorbed radiation doses (mGy/MBq) from intravenous injection of Sodium Fluoride F 18 Injection, USP are shown in Table 1. These estimates were calculated based on human data and using the data published by the Nuclear Regulatory Commission  and International Commission on Radiological Protection for Sodium Fluoride Injection . The bone, bone marrow and urinary bladder are considered target and critical organs.
|Organ||Estimated Radiation Dose mGy/MBq|
70 kg 
56.8 kg 
33.2 kg 
19.8 kg 
9.7 kg 
|Upper large intestine wall||0.0058||0.010||0.016||0.026||0.046|
|Lower large intestine wall||0.0012||0.016||0.025||0.037||0.063|
|Urinary bladder wall||0.25||0.27||0.4||0.61||1.1|
|Effective Dose Equivalent (mSv/MBq)||0.027||0.034||0.052||0.086||0.17|
 Data from Nuclear Regulatory Commission Report, Radiation Dose Estimates for Radiopharmaceuticals, NUREG/CR-6345, page 10, 1996.
 Data from ICRP publication 53, Radiation Dose to Patients from Radiopharmaceuticals, Ann ICRP, Volume 18, pages 15 and 74, 1987.
Multiple-dose vial containing 370-7,400 MBq/mL (10-200 mCi/mL) at EOS reference time of no-carrier-added sodium fluoride F18 in aqueous 0.9% sodium chloride solution. Sodium Fluoride F 18 Injection USP is a clear, colorless, sterile, pyrogen-free and preservative-free solution for intravenous administration.
As with any injectable drug product, allergic reactions and anaphylaxis may occur. Emergency resuscitation equipment and personnel should be immediately available.
Sodium Fluoride F 18 Injection USP may increase the risk of cancer. Carcinogenic and mutagenic studies with Sodium Fluoride F18 injection USP have not been performed. Use the smallest dose necessary for imaging and ensure safe handling to protect the patient and health care worker [see Dosage and Administration (2.1)].
No adverse reactions have been reported for Sodium Fluoride F 18 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.
The possibility of interactions of Sodium Fluoride F 18 Injection USP with other drugs taken by patients undergoing PET imaging has not been studied.
Pregnancy Category C
Any radiopharmaceutical including Sodium Fluoride F18 Injection USP has a potential to cause fetal harm. The likelihood of fetal harm depends on the stage of fetal development, and the radionuclide dose. Animal reproduction studies have not been conducted with Sodium Fluoride F 18 Injection USP. Prior to the administration of Sodium Fluoride F 18 Injection USP to women of childbearing potential, assess for presence of pregnancy. Sodium Fluoride F 18 Injection USP should be given to a pregnant woman only if clearly needed.
It is not known whether Sodium Fluoride F 18 Injection USP is excreted into human milk. Because many drugs are excreted in human milk and because of the potential for serious adverse reactions in nursing infants, a decision should be made whether to interrupt nursing after administration of Sodium Fluoride F 18 Injection USP or not to administer Sodium Fluoride F 18 Injection USP, taking into account the importance of the drug to the mother. The body of scientific information related to radioactivity decay, drug tissue distribution and drug elimination shows that less than 0.01% of the radioactivity administered remains in the body after 24 hours (10 half-lives). To minimize the risks to a nursing infant, interrupt nursing for at least 24 hours.
In reported clinical experience in approximately 100 children, weight based doses (2.1 MBq/kg) ranging from 19 MBq – 148 MBq (0.5 mCi - 4 mCi) were used. Sodium Fluoride F18 was shown to localize to areas of bone turnover including rapidly growing epiphyses in developing long bones. Children are more sensitive to radiation and may be at higher risk of cancer from Sodium Fluoride F18 injection USP.
Sodium Fluoride F 18 Injection USP is a positron emitting radiopharmaceutical, containing no-carrier-added, radioactive fluoride F 18 that is used for diagnostic purposes in conjunction with PET imaging. It is administered by intravenous injection. The active ingredient, sodium fluoride F 18, has the molecular formula Na[18F] with a molecular weight of 40.99, and has the following chemical structure:
Na+ 18 F-
Sodium Fluoride F 18 Injection USP is provided as a ready-to-use, isotonic, sterile, pyrogen-free, preservative-free, clear and colorless solution. Each mL of the solution contains between 370 MBq to 7,400 MBq (10 mCi to 200 mCi) sodium fluoride F 18, at the EOS reference time, in 0.9% aqueous sodium chloride. The pH of the solution is between 4.5 and 8. The solution is presented in 30 mL multiple- dose glass vials with variable total volume and total radioactivity in each vial.
Fluoride F 18 decays by positron (β+) emission and has a half-life of 109.7 minutes. Ninety-seven percent of the decay results in emission of a positron with a maximum energy of 633 keV and 3% of the decay results in electron capture with subsequent emission of characteristic X-rays of oxygen. The principal photons useful for diagnostic imaging are the 511 keV gamma photons, resulting from the interaction of the emitted positron with an electron (Table 2). Fluorine F 18 atom decays to stable 18O-oxygen.
|Radiation/Emission||% per Disintegration||Mean Energy|
|Positron (β+)||96.73||249.8 keV|
|Gamma (±)*||193.46||511.0 keV|
The specific gamma ray constant (point source air kerma coefficient) for fluoride F18 is 5.7 R/hr/mCi (1.35 x 10 -6 Gy/hr/kBq) at 1 cm. The half-value layer (HVL) for the 511 keV photons is 4 mm lead (Pb). A range of values for the attenuation of radiation results from the interposition of various thickness of Pb. The range of attenuation coefficients for this radionuclide is shown in Table 3. For example, the interposition of an 8 mm thickness of Pb with a coefficient of attenuation of 0.25 will decrease the external radiation by 75%.
|Shield Thickness (Pb) mm||Coefficient of Attenuation|
Table 4 lists the fraction of radioactivity remaining at selected time intervals from the calibration time. This information may be used to correct for physical decay of the radionuclide.
|Time Since Calibration||Fraction Remaining|
Fluoride F 18 ion normally accumulates in the skeleton in an even fashion, with greater deposition in the axial skeleton (e.g. vertebrae and pelvis) than in the appendicular skeleton and greater deposition in the bones around joints than in the shafts of long bones.
Increased fluoride F18 ion deposition in bone can occur in areas of increased osteogenic activity during growth, infection, malignancy (primary or metastatic) following trauma, or inflammation of bone.
After intravenous administration, fluoride F 18 ion is rapidly cleared from the plasma in a biexponential manner. The first phase has a half-life of 0.4 h, and the second phase has a half-life of 2.6 h. Essentially all the fluoride F 18 that is delivered to bone by the blood is retained in the bone. One hour after administration of fluoride F 18 only about 10% of the injected dose remains in the blood. Fluoride F 18 diffuses through capillaries into bone extracellular fluid space, where it becomes bound by chemisorption at the surface of bone crystals, preferentially at sites of newly mineralizing bone.
Deposition of fluoride F 18 in bone appears to be primarily a function of blood flow to the bone and the efficiency of the bone in extracting the fluoride F 18. Fluoride F 18 does not appear to be bound to serum proteins.
In patients with normal renal function, 20% or more of the fluorine ion is cleared from the body in the urine within the first 2 hours after intravenous administration.
The doses used in reported studies ranged from 2.7 mCi to 20 mCi (100 MBq to 740 MBq), with an average median dose of 10 mCi (370 MBq) and an average mean dose of 9.2 mCi (340 MBq). In PET imaging of bone metastases with Sodium Fluoride F 18 Injection USP, focally increased tracer uptake is seen in both osteolytic and osteoblastic bone lesions. Negative PET imaging results with Sodium Fluoride F 18 Injection USP do not preclude the diagnosis of bone metastases. Also, as benign bone lesions are also detected by Sodium Fluoride F 18 Injection USP, positive PET imaging results cannot replace biopsy to confirm a diagnosis of cancer.
Sodium Fluoride F 18 Injection USP is supplied in a multiple-dose Type I glass vial with (elastomeric) stopper and aluminum crimp seal containing between 370 and 7,400 MBq/mL (10-200 mCi/mL) of no-carrier-added sodium fluoride F 18, at the EOS reference time, in aqueous 0.9% sodium chloride solution. The total volume and total radioactivity per vial are variable. Each vial is enclosed in a shielding container of appropriate thickness.
The product is available in a 30 mL vial configuration with a variable fill volume. The NDC number is:
51760-002-30 (30 mL)
Store at 25°C (77°F); excursions permitted to 15–30°C (59–86°F). Use the solution within 12 hours of the EOS reference time.
Encourage patients to drink at least 500 mL of water prior to drug administration.
To help protect themselves and others in their environment, patients should take the following precautions for 12 hours after injection: whenever possible, use a toilet and flush several times after each use; wash hands thoroughly after each voiding or fecal elimination. If blood, urine or feces soil clothing, wash the clothing separately.
sodium fluoride f-18 injection
|Labeler - Essential Isotopes LLC (010753961)|
|Essential Isotopes LLC||010753961||positron emission tomography drug production(51760-002)|