SODIUM FLUORIDE F 18 injection

Sodium Fluoride by

Drug Labeling and Warnings

Sodium Fluoride by is a Prescription medication manufactured, distributed, or labeled by THE FEINSTEIN INSTITUTES FOR MEDICAL RESEARCH. Drug facts, warnings, and ingredients follow.

Drug Details [pdf]

  • 1 INDICATIONS AND USAGE

    Sodium Fluoride F 18 Injection, USP is indicated for diagnostic positron emission tomography (PET) imaging of bone to define areas of altered osteogenic activity.

  • 2 DOSAGE AND ADMINISTRATION

    2.1 Radiation Safety - Drug Handling

    Wear waterproof gloves and effective shielding when handling Sodium Fluoride F 18 Injection, USP. 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.

    Use aseptic technique to maintain sterility during all operations involved in the manipulation and administration of Sodium Fluoride F 18 Injection, USP.

    The dose of Sodium Fluoride F 18 Injection, USP should be minimized consistent with the objectives of the procedure, and the nature of the radiation detection devices employed.

    The final dose for the patient should be calculated using proper decay factors from the time of End of Synthesis (EOS), and measured by a suitable radioactivity calibration system before administration [see Description (11.2)].

    2.2 Radiation Safety - Patient Preparation

    To minimize radiation-absorbed dose to the bladder, encourage adequate hydration. Encourage the patient to ingest at least 500 mL of fluid immediately prior and subsequent to the administration of Sodium Fluoride F 18 Injection, USP.

    Encourage the patient to void one-half hour after administration of Sodium Fluoride F 18 Injection, USP and as frequently thereafter as possible for the next 12 hours.

    2.3 Drug Preparation and Administration

    Calculate the necessary volume to administer based on calibration time and dose.

    Inspect Sodium Fluoride F 18 Injection, USP visually for particulate matter and discoloration before administration, whenever solution and container permit.

    Do not administer Sodium Fluoride F 18 Injection, USP containing particulate matter or discoloration; dispose of these unacceptable or unused preparations in a safe manner, in compliance with applicable regulations.

    Aseptically withdraw Sodium Fluoride F 18 Injection, USP from its container.

    2.4 Recommended Dose for Adults

    Administer 296-444 MBq (8-12 mCi) as an intravenous injection.

    2.5 Recommended Dose for Pediatric Patients

    In reported clinical experience in approximately 100 children, weight based doses (2.1 MBq/kg) ranging from 18.5 MBq-148 MBq (0.5 mCi-4 mCi) were used.

    2.6 Radiation Dosimetry

    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 [1] and the International Commission on Radiological Protection for Sodium Fluoride Injection [2]. The bone, bone marrow, and urinary bladder are considered target and critical organs.

    Table 1. Estimated Absorbed Radiation Doses after Intravenous Administration of Sodium Fluoride F 18 Injection, USP
    Organ Estimated Radiation Dose mGy/MBq

                                  Adult

                                  70 kg [1]

    15 year

    56.8 kg [2]

              10 year              

              33.2 kg [2]

    5 year              

    19.8 kg [2]

    1 year 

    9.7 kg [2]
    Adrenals                                0.0062    0.012              0.018    0.028  0.052
    Brain                                                                     0.0056     N/A               N/A     N/A   N/A
    Bone surfaces                                 0.060    0.050              0.079     0.13   0.30
    Breasts                                0.0028   0.0061             0.0097    0.015  0.030
    Gallbladder wall                                0.0044     N/A               N/A     N/A   N/A
    Stomach wall                                 0.0038    0.008              0.013    0.019  0.036
    Small intestine                                0.0066    0.012              0.018    0.028  0.052
    Upper large intestine wall                                0.0058    0.010              0.016    0.026  0.046
    Lower large intestine wall                                 0.012    0.016              0.025    0.037  0.063
    Heart wall                                0.0039     N/A               N/A     N/A   N/A
    Kidneys                                 0.019    0.025              0.036    0.053  0.097
    Liver                                0.0040   0.0084              0.013    0.021  0.039
    Lungs                                0.0041   0.0084              0.013    0.020  0.039
    Muscle                                0.0060     N/A               N/A     N/A   N/A
    Ovaries                                 0.011    0.016              0.023    0.036  0.063
    Pancreas                                0.0048   0.0096              0.015    0.023  0.044
    Red marrow                                 0.028    0.053              0.088     0.18   0.38
    Skin                                0.0040     N/A               N/A     N/A   N/A
    Spleen                                0.0042   0.0088              0.014    0.021  0.041
    Testes                                0.0078    0.013              0.021    0.033  0.062
    Thymus                                0.0035     N/A               N/A     N/A   N/A
    Thyroid                                0.0044   0.0084              0.013    0.020  0.036
    Urinary bladder wall                                  0.25     0.27                0.4     0.61    1.1
    Uterus                                 0.019    0.023              0.037    0.057  0.099
    Other tissue                                  N/A    0.010              0.015    0.024  0.044
    Effective Dose Equivalent mSv/MBq                                  0.027    0.034              0.052    0.086   0.17

    [1] Data from Nuclear Regulatory Commission Report, Radiation Dose Estimates for Radiopharmaceuticals, NUREG/CR-6345, page 10, 1996.
    [2] Data from ICRP publication 53, Radiation Dose to Patients from Radiopharmaceuticals, Ann ICRP, Volume 18, pages 15 and 74, 1987.

    2.7 Imaging Guidelines

    Imaging of Sodium Fluoride F 18 Injection, USP can begin 1-2 hours after administration; optimally at 1 hour post administration.

    Encourage the patient to void immediately prior to imaging the fluoride F 18 radioactivity in the lumbar spine or bony pelvis.

  • 3 DOSAGE FORMS AND STRENGTHS

    Multiple-dose vial containing 740-22,200 MBq/mL (20-600 mCi/mL) at EOS reference time of no-carrier-added sodium fluoride F 18 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.

  • 4 CONTRAINDICATIONS

    None.

  • 5 WARNINGS AND PRECAUTIONS


    5.1 Allergic Reactions

    As with any injectable drug product, allergic reactions and anaphylaxis may occur. Emergency resuscitation equipment and personnel should be immediately available.

    5.2 Radiation Risks

    Sodium Fluoride F 18 Injection, USP may increase the risk of cancer. Carcinogenic and mutagenic studies with Sodium Fluoride F 18 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)].

  • 6 ADVERSE REACTIONS

    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.

  • 7 DRUG INTERACTIONS

    The possibility of interactions of Sodium Fluoride F 18 Injection, USP with other drugs taken by patients undergoing PET imaging has not been studied.

  • 8 USE IN SPECIFIC POPULATIONS


    8.1 Pregnancy

    Pregnancy Category C
    Any radiopharmaceutical including Sodium Fluoride F 18 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 reproductive and developmental toxicity 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.

    8.3 Nursing Mothers

    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 radioactive decay, drug tissue distribution, and drug elimination shows that less than 0.01% of the radioactivity administered remains in the body after 24 hours (12 half-lives). To minimize the risks to a nursing infant, interrupt nursing for at least 24 hours.

    8.4 Pediatric Use

    In reported clinical experience in approximately 100 children, weight based doses (2.1 MBq/kg) ranging from 18.5 MBq-148 MBq (0.5 mCi-4 mCi) were used. Sodium Fluoride F 18 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 F 18 Injection, USP.

  • 11 DESCRIPTION


    11.1 Chemical Characteristics

    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+18F-


    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 740 MBq to 22,200 MBq (20 mCi to 600 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 25 mL multiple-dose glass vials with variable total volume and total radioactivity in each vial.

    11.2 Physical Characteristics

    Fluorine 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.

    Table 2. Principal Emission Data for Fluoride F 18
    Radiation/Emission                    % per Disintegration                   Mean Energy
          Positron (β+)            96.73  249.8 keV
          Gamma (±)*           193.46  511.0 keV

    *Produced by positron annihilation
    [3] Kocher, D.C. Radioactive Decay Data Tables DOE/TIC-11026, 69, 1981.

    The specific gamma ray constant for fluoride F 18 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 4.1 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 8.3 mm thickness of Pb with a coefficient of attenuation of 0.25 will decrease the external radiation by 75%.

    Table 3. Radiation Attenuation of 511 keV Photons by Lead (Pb) Shielding
            Shield Thickness (Pb) mm         Coefficient of Attenuation
                                  0                           0.00
                                  4                           0.50
                                  8                           0.25
                                 13                           0.10
                                 26                           0.01
                                 39                          0.001
                                 52                         0.0001


    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.

    Table 4. Physical Decay Chart for Fluoride F 18
                                 Time Since Calibration           Fraction Remaining
                                                  0*                         1.00
                                            15 minutes                        0.909
                                            30 minutes                        0.826
                                            60 minutes                        0.683
                                           110 minutes                        0.500
                                           220 minutes                        0.250
                                           440 minutes                        0.060
                                              12 hours                        0.011
                                              24 hours                       0.0001

    *Calibration time

  • 12 CLINICAL PHARMACOLOGY


    12.1 Mechanism of Action

    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.

    12.2 Pharmacodynamics

    Increased fluoride F 18 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.

    12.3 Pharmacokinetics

    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.

  • 13 NONCLINICAL TOXICOLOGY


    13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility

    Studies to assess reproductive toxicity, mutagenesis, and carcinogenesis potential of Sodium Fluoride F 18 Injection, USP have not been performed.

  • 14 CLINICAL STUDIES


    14.1 Metastatic Bone Disease

    The doses used in reported studies ranged from 2.7 mCi to 20 mCi (99.9 MBq to 740 MBq), with an average median dose of 10 mCi (370 MBq) and an average mean dose of 9.2 mCi (340.4 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.

    14.2 Other Bone Disorders

    The doses used in reported studies ranged from 2.43 mCi to 15 mCi (89.9 MBq to 555 MBq), with an average median dose of 8.0 mCi (296 MBq) and an average mean dose of 7.6 mCi (281.2 MBq).

  • 15 REFERENCES

    1. Stabin, M.G., Stubbs, J. B., and Toohey R. E., Radiation Dose Estimates for Radiopharmaceuticals, U.S. Nuclear Regulatory Commission report NUREG/CR-6345, page 10, 1996.
    2. Radiation Dose to Patients from Radiopharmaceuticals, ICRP publication 53, Ann ICRP, 18, pages 15 and 74, 1987.
    3. Kocher, D. C., “Radioactive Decay Data Tables: A Handbook of decay data for application to radiation dosimetry and radiological assessments” DOE/TIC-11026, page 69, 1981.

  • 16 HOW SUPPLIED/STORAGE AND HANDLING

    Sodium Fluoride F 18 Injection, USP is supplied in a multiple-dose Type 1 glass vial with elastomeric stopper and aluminum crimp seal containing between 740 and 22,200 MBq/mL (20-600 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 shielded container of appropriate thickness. The product is available in a 25 mL vial configuration with a variable fill volume. The NDC number is: 13267-542-42.

    Storage
    Store at 25°C (77°F) in a shielded container; excursions permitted to 15-30°C (59-86°F). Use the solution within 12 hours of the EOS reference time.

    Handling
    Receipt, transfer, handling, possession, or use of this product is subject to the radioactive material regulations and licensing requirements of the U.S. Nuclear Regulatory Commission, Agreement States or Licensing States as appropriate.

  • 17 PATIENT COUNSELING INFORMATION


    17.1 Pre-study Hydration

    Encourage patients to drink at least 500 mL of water prior to drug administration.

    17.2 Post-study Voiding

    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.

  • SPL UNCLASSIFIED SECTION

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

  • PRINCIPAL DISPLAY PANEL

    Sodium Fluoride F 18 Injection, USP
    740 MBq/mL to 22,200 MBq/mL (20 mCi/mL to 600 mCi/mL) at End of Synthesis (EOS)
    Diagnostic – For Intravenous Use Only
    Sterile, Non-pyrogenic
    NDC# 13267-542-42
    25 mL Multiple-Dose Vial
    CAUTION: RADIOACTIVE MATERIAL RX ONLY
    Manufactured by The Feinstein Institutes for Medical Research, Manhasset, NY 11030

    NAF Vial Label

    NAF Lead Pig Label

  • INGREDIENTS AND APPEARANCE
    SODIUM FLUORIDE  F 18
    sodium fluoride f 18 injection
    Product Information
    Product TypeHUMAN PRESCRIPTION DRUGItem Code (Source)NDC: 13267-542
    Route of AdministrationINTRAVENOUS
    Active Ingredient/Active Moiety
    Ingredient NameBasis of StrengthStrength
    SODIUM FLUORIDE F-18 (UNII: 9L75099X6R) (FLUORIDE ION F-18 - UNII:4M4WE5N2GE) FLUORIDE ION F-18600 mCi  in 1 mL
    Inactive Ingredients
    Ingredient NameStrength
    SODIUM CHLORIDE (UNII: 451W47IQ8X) 9 mg  in 1 mL
    Packaging
    #Item CodePackage DescriptionMarketing Start DateMarketing End Date
    1NDC: 13267-542-4220 mL in 1 VIAL, GLASS; Type 0: Not a Combination Product11/19/2014
    Marketing Information
    Marketing CategoryApplication Number or Monograph CitationMarketing Start DateMarketing End Date
    ANDAANDA20432811/19/2014
    Labeler - THE FEINSTEIN INSTITUTES FOR MEDICAL RESEARCH (110565913)
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