REFERENCES SECTION.

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, 19873.Kocher, D.C., Radioactive Decay Data Tables: Handbook of decay data for application to radiation dosimetry and radiological assessments DOE/TIC-11026, page 69, 1981.. 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: Handbook of decay data for application to radiation dosimetry and radiological assessments DOE/TIC-11026, page 69, 1981.

DOSAGE FORMS & STRENGTHS SECTION.

3 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. Sodium Fluoride F-18 Injection, USP, is clear, colorless, sterile, pyrogen-free and preservative-free solution for intravenous administration.. Multiple-dose vial containing 370-7,400 MBq/mL (10-200 mCi/mL) of no-carrier-added sodium fluoride F-18 at the end of synthesis (EOS) reference time in aqueous 0.9% sodium chloride solution (3). Sodium Fluoride F-18 Injection, USP, is clear, colorless, sterile, pyrogen-free and preservative-free solution for intravenous administration.

DRUG INTERACTIONS SECTION.

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.

ADVERSE REACTIONS SECTION.

6 ADVERSE REACTIONS. No adverse reactions have been reported for Sodium Fluoride F-18 Injection, USP, based on 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 Sodium Fluoride F-18 Injection, USP, based on review of the published literature, publicly available reference sources, and adverse drug reaction reporting systems (6). To report SUSPECTED ADVERSE REACTIONS, contact Cardinal Health at 1-800-618-2768 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

CARCINOGENESIS & MUTAGENESIS & IMPAIRMENT OF FERTILITY SECTION.

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.

CLINICAL PHARMACOLOGY SECTION.

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 biexponential manner. The first phase has half-life of 0.4 h, and the second phase has 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 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 hours after intravenous administration.

CLINICAL STUDIES SECTION.

14 CLINICAL STUDIES. 14.1 Metastatic Bone Disease. 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 diagnosis of cancer.. 14.2 Other Bone Disorders. The doses used in reported studies ranged from 2.43 mCi to 15 mCi (90 MBq to 555 MBq), with an average median dose of 8.0 mCi (300 MBq) and an average mean dose of 7.6 mCi (280 MBq).

CONTRAINDICATIONS SECTION.

4 CONTRAINDICATIONS. None. None (4).

DESCRIPTION SECTION.

11 DESCRIPTION. 11.1 Chemical Characteristics. Sodium Fluoride F-18 Injection, USP, is 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 molecular weight of 40.99, and has the following chemical structure:Na+18F- Sodium Fluoride F-18 Injection, USP, is provided as 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.. 11.2 Physical Characteristics. Fluoride F-18 decays by positron (+) emission and has half-life of 109.7 minutes. Ninety-seven percent of the decay results in emission of positron with 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(+)96.73249.8 keVGamma(+-)Produced by positron annihilationFrom: Kocher, D.C. Radioactive Decay Data Tables DOE/TIC-11026, 69, 1981 193.46511.0 keVThe specific gamma ray constant for fluoride F-18 is 5.7 R/hr/mCi (1.35 10-6 Gy/hr/kBq) at cm. The half-value layer (HVL) for the 511 keV photons is 4.1 mm lead (Pb) or 2.9 mm tungsten (W) alloy. range of values for the attenuation of radiation results from the interposition of various thickness of Pb or Tungsten alloy. 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 or 5.8 mm thickness of alloy with coefficient of attenuation of 0.25 will decrease the external radiation by 75%.Table 3. Radiation Attenuation of 511 keV Photons by lead (Pb) and Tungsten (W) alloy shielding Shield Thickness (Pb) mm Shield Thickness (W) Alloy mm Coefficient of Attenuation000.00430.50860.251390.1026190.0139280.00153370.0001Table 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 0calibration time 1.0015 minutes0.90930 minutes0.82660 minutes0.683110 minutes0.500220 minutes0.250440 minutes0.06012 hours0.01124 hours0.0001.

DOSAGE & ADMINISTRATION SECTION.

2 DOSAGE AND ADMINISTRATION. oSodium Fluoride F-18 Injection, USP, emits radiation and must be handled with appropriate safety measures (2.1).oAdminister 300-450 MBq (8-12 mCi) as an intravenous injection in adults (2.4).oAdminister approximately 2.1 MBq/kg in children with minimum of 19 MBq (0.5 mCi) and maximum of 148 MBq (4 mCi) as an intravenous injection (2.5).oImaging can begin 1-2 hours after administration; optimally at one hour post administration (2.7).oEncourage patients to void immediately prior to imaging the lumbar spine and bony pelvis (2.7).. oSodium Fluoride F-18 Injection, USP, emits radiation and must be handled with appropriate safety measures (2.1).. oAdminister 300-450 MBq (8-12 mCi) as an intravenous injection in adults (2.4).. oAdminister approximately 2.1 MBq/kg in children with minimum of 19 MBq (0.5 mCi) and maximum of 148 MBq (4 mCi) as an intravenous injection (2.5).. oImaging can begin 1-2 hours after administration; optimally at one hour post administration (2.7).. oEncourage patients to void immediately prior to imaging the lumbar spine and bony pelvis (2.7).. 2.1 Radiation Safety Drug Handling. oWear 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.oRadiopharmaceuticals 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.oUse aseptic technique to maintain sterility during all operations involved in the manipulation and administration of Sodium Fluoride F-18 Injection, USP.oThe 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.oThe final dose for the patient should be calculated using proper decay factors from the time of End of Synthesis (EOS), and measured by suitable radioactivity calibration system before administration [see Description (11.2)].. oWear 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.. oRadiopharmaceuticals 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.. oUse aseptic technique to maintain sterility during all operations involved in the manipulation and administration of Sodium Fluoride F-18 Injection, USP.. oThe 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.. oThe final dose for the patient should be calculated using proper decay factors from the time of End of Synthesis (EOS), and measured by suitable radioactivity calibration system before administration [see Description (11.2)].. 2.2 Radiation Safety Patient Preparation. oTo minimize the 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.oEncourage 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.. oTo minimize the 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.. oEncourage 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. oCalculate the necessary volume to administer based on calibration time and dose. oInspect Sodium Fluoride F-18 Injection, USP, visually for particulate matter and discoloration before administration, whenever solution and container permit.oDo not administer Sodium Fluoride F-18 Injection, USP, containing particulate matter or discoloration; dispose of these unacceptable or unused preparations in safe manner, in compliance with applicable regulations.oAseptically withdraw Sodium Fluoride F-18 Injection, USP, from its container.. oCalculate the necessary volume to administer based on calibration time and dose. oInspect Sodium Fluoride F-18 Injection, USP, visually for particulate matter and discoloration before administration, whenever solution and container permit.. oDo not administer Sodium Fluoride F-18 Injection, USP, containing particulate matter or discoloration; dispose of these unacceptable or unused preparations in safe manner, in compliance with applicable regulations.. oAseptically withdraw Sodium Fluoride F-18 Injection, USP, from its container.. 2.4 Recommended Dose for Adults. Administer 300-450 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 19 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, USPOrganEstimated Radiation Dose mGy/MBqAdult 70 kgData from Nuclear Regulatory Commission Report, Radiation Dose Estimates for Radiopharmaceuticals, NUREG/CR-6345, page 10, 1996. 15 year 56.8 kgData from ICRP publication 53, Radiation Dose to Patients from Radiopharmaceuticals, Ann ICRP, Volume 18, pages 15 and 74, 1987. 10 year 33.2 kg year 19.8 kg year 9.7 kg Adrenals0.00620.0120.0180.0280.052Brain0.0056N/AN/AN/AN/ABone surfaces0.0600.0500.0790.130.30Breasts0.00280.00610.00970.0150.030GI Gallbladder wall0.0044N/AN/AN/AN/A Stomach wall0.00380.0080.0130.0190.036 Small intestine0.00660.0120.0180.0280.052 Upper large intestine wall0.00580.0100.0160.0260.046 Lower large intestine wall 0.0120.0160.0250.0370.063Heart wall0.0039N/AN/AN/AN/AKidneys0.0190.0250.0360.0530.097Liver0.00400.00840.0130.0210.039Lungs0.00410.00840.0130.0200.039Muscle0.0060N/AN/AN/AN/AOvaries0.0110.0160.0230.0360.063Pancreas0.00480.00960.0150.0230.044Red marrow0.0280.0530.0880.180.38Skin0.0040N/AN/AN/AN/ASpleen0.00420.00880.0140.0210.041Testes0.00780.0130.0210.0330.062Thymus0.0035N/AN/AN/AN/AThyroid0.00440.00840.0130.0200.036Urinary bladder wall0.250.270.40.611.1Uterus0.0190.0230.0370.0570.099Other tissueN/A0.0100.0150.0240.044Effective Dose Equivalent mSv/MBq0.0270.0340.0520.0860.17. 2.7 Imaging Guidelines. oImaging of Sodium Fluoride F-18 Injection, USP, can begin 1-2 hours after administration; optimally at hour post administration. oEncourage the patient to void immediately prior to imaging the fluoride F-18 radioactivity in the lumbar spine or bony pelvis.. oImaging of Sodium Fluoride F-18 Injection, USP, can begin 1-2 hours after administration; optimally at hour post administration. oEncourage the patient to void immediately prior to imaging the fluoride F-18 radioactivity in the lumbar spine or bony pelvis.

HOW SUPPLIED SECTION.

16 HOW SUPPLIED/STORAGE AND HANDLING. Sodium Fluoride F-18 Injection, USP, is supplied in multiple-dose Type 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 shielded container of appropriate thickness.The product is available in 30 mL vial configuration with variable fill volume. The NDC number is:NDC 65857-300-30StorageStore at 25C (77F) in shielded container; excursions permitted to 15-30C (59-86F). Use the solution within 12 hours of the EOS reference time.HandlingReceipt, 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.

INDICATIONS & USAGE SECTION.

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.. Sodium Fluoride F-18 Injection, USP, is radioactive diagnostic agent for positron emission tomography (PET) indicated for imaging of bone to define areas of altered osteogenic activity (1).

INFORMATION FOR PATIENTS SECTION.

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 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.Manufactured by: Cardinal Health 414, LLC7000 Cardinal PlaceDublin, OH 43017Distributed by: Cardinal Health 414, LLC7000 Cardinal PlaceDublin, OH 43017.

MECHANISM OF ACTION SECTION.

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.

NONCLINICAL TOXICOLOGY SECTION.

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.

NURSING MOTHERS SECTION.

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, 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 nursing infant, interrupt nursing for at least 24 hours.

PACKAGE LABEL.PRINCIPAL DISPLAY PANEL.

PRINCIPAL DISPLAY PANEL CARTON LABEL Carton LabelNDC 65857-300-30Sodium Fluoride F-18 Injection, USP10 200 mCi/mL at End of Synthesis (EOS)Diagnostic For Intravenous Use OnlyLot EOS Date: // EOS Time: Activity EOS: mCiConcentration: mCi/mL Volume: mLExp. Date: // Exp. Time: Each mL Contains:0.37 to 7.4 GBq (10 to 200 mCi) of no-carrier added sodium [18F]fluoride in aqueous 0.9% sodium chloride solution at EOS. Use within 12 hours of EOS.Store at 25C (77F); excursions permitted to 15-30C (59-86F) [see USP controlled roomtemperature]. Store upright in shielded container. Aseptically withdraw and handle doses.Do not use if cloudy or if it contains particulate matter.Calculate correct dosage from date and time of calibration.Sterile, Non-pyrogenic 30 mL Multiple-Dose Vial 18F Half-life 109.7 min Rx ONLYCAUTION:RADIOACTIVE MATERIALManufactured and Distributed by:Cardinal Health 414, LLC7000 Cardinal Place, Dublin, OH 43017. Principal Display Panel Carton Label.

PEDIATRIC USE SECTION.

8.4 Pediatric Use. 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 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.

PHARMACODYNAMICS SECTION.

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.

PHARMACOKINETICS SECTION.

12.3 Pharmacokinetics. After intravenous administration, fluoride F-18 ion is rapidly cleared from the plasma in biexponential manner. The first phase has half-life of 0.4 h, and the second phase has 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 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 hours after intravenous administration.

PREGNANCY SECTION.

8.1 Pregnancy. Pregnancy Category C. Any radiopharmaceutical including Sodium Fluoride F-18 Injection, USP, has 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 pregnant woman only if clearly needed.

SPL UNCLASSIFIED SECTION.

2.1 Radiation Safety Drug Handling. oWear 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.oRadiopharmaceuticals 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.oUse aseptic technique to maintain sterility during all operations involved in the manipulation and administration of Sodium Fluoride F-18 Injection, USP.oThe 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.oThe final dose for the patient should be calculated using proper decay factors from the time of End of Synthesis (EOS), and measured by suitable radioactivity calibration system before administration [see Description (11.2)].. oWear 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.. oRadiopharmaceuticals 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.. oUse aseptic technique to maintain sterility during all operations involved in the manipulation and administration of Sodium Fluoride F-18 Injection, USP.. oThe 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.. oThe final dose for the patient should be calculated using proper decay factors from the time of End of Synthesis (EOS), and measured by suitable radioactivity calibration system before administration [see Description (11.2)].

USE IN SPECIFIC POPULATIONS SECTION.

8 USE IN SPECIFIC POPULATIONS. oPregnancy: No human or animal data. Any radiopharmaceutical, including Sodium Fluoride F-18 Injection, USP, may cause fetal harm. Use only if clearly needed (8.1)oNursing: decision should be made whether to interrupt nursing after Sodium Fluoride F-18 Injection, USP, administration or not to administer Sodium Fluoride F-18 Injection, USP, taking into consideration the importance of the drug to the mother. (8.3)oPediatrics: Children are more sensitive to radiation and may be at higher risk of cancer from Sodium Fluoride F-18 Injection, USP (8.4).. oPregnancy: No human or animal data. Any radiopharmaceutical, including Sodium Fluoride F-18 Injection, USP, may cause fetal harm. Use only if clearly needed (8.1). oNursing: decision should be made whether to interrupt nursing after Sodium Fluoride F-18 Injection, USP, administration or not to administer Sodium Fluoride F-18 Injection, USP, taking into consideration the importance of the drug to the mother. (8.3). oPediatrics: Children are more sensitive to radiation and may be at higher risk of cancer from Sodium Fluoride F-18 Injection, USP (8.4).. 8.1 Pregnancy. Pregnancy Category C. Any radiopharmaceutical including Sodium Fluoride F-18 Injection, USP, has 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 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, 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 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 19 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.

WARNINGS AND PRECAUTIONS SECTION.

5 WARNINGS AND PRECAUTIONS. oAllergic Reactions: As with any injectable drug product, allergic reactions and anaphylaxis may occur. Emergency resuscitation equipment and personnel should be immediately available (5.1).oCancer Risk: Sodium Fluoride F-18 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 (5.2).. oAllergic Reactions: As with any injectable drug product, allergic reactions and anaphylaxis may occur. Emergency resuscitation equipment and personnel should be immediately available (5.1).. oCancer Risk: Sodium Fluoride F-18 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 (5.2).. 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)].