ADVERSE REACTIONS SECTION.

6 ADVERSE REACTIONS. No adverse reactions have been reported for Sodium Fluoride 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 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 Essential Isotopes LLC at 1-573-882-0245 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 18 Injection USP have not been performed.

CLINICAL PHARMACOLOGY SECTION.

12 CLINICAL PHARMACOLOGY. 12.1 Mechanism of Action. Fluoride 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 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.. 12.3 Pharmacokinetics. After intravenous administration, fluoride 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 18 that is delivered to bone by the blood is retained in the bone. One hour after administration of fluoride 18 only about 10% of the injected dose remains in the blood. Fluoride 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 18 in bone appears to be primarily function of blood flow to the bone and the efficiency of the bone in extracting the fluoride 18. Fluoride 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 18 Injection USP, focally increased tracer uptake is seen in both osteolytic and osteoblastic bone lesions. Negative PET imaging results with Sodium Fluoride 18 Injection USP do not preclude the diagnosis of bone metastases. Also, as benign bone lesions are also detected by Sodium Fluoride 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).

PHARMACOKINETICS SECTION.

12.3 Pharmacokinetics. After intravenous administration, fluoride 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 18 that is delivered to bone by the blood is retained in the bone. One hour after administration of fluoride 18 only about 10% of the injected dose remains in the blood. Fluoride 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 18 in bone appears to be primarily function of blood flow to the bone and the efficiency of the bone in extracting the fluoride 18. Fluoride 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 CAny radiopharmaceutical including Sodium Fluoride F18 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 reproduction studies have not been conducted with Sodium Fluoride 18 Injection USP. Prior to the administration of Sodium Fluoride 18 Injection USP to women of childbearing potential, assess for presence of pregnancy. Sodium Fluoride 18 Injection USP should be given to pregnant woman only if clearly needed.

DESCRIPTION SECTION.

11 DESCRIPTION. 11.1 Chemical Characteristics. Sodium Fluoride 18 Injection USP is positron emitting radiopharmaceutical, containing no-carrier-added, radioactive fluoride 18 that is used for diagnostic purposes in conjunction with PET imaging. It is administered by intravenous injection. The active ingredient, sodium fluoride 18, has the molecular formula Na[18F] with molecular weight of 40.99, and has the following chemical structure:Na+ 18 F- Sodium Fluoride 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 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 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 18 atom decays to stable 18O-oxygen.Table 2: Principal Emission Data for Fluoride 18 Radiation/Emission% per DisintegrationMean EnergyPositron (+)96.73249.8 keVGamma (+-)Produced by positron annihilation[3] Kocher, D.C. Radioactive Decay Data Tables DOE/TIC-11026, 69, 1981. 193.46511.0 keVThe specific gamma ray constant (point source air kerma coefficient) for fluoride F18 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 mm lead (Pb). 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 mm thickness of Pb 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) ShieldingShield Thickness (Pb) mmCoefficient of Attenuation00.0040.5080.25130.10260.01390.001520.0001Table 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 18Time Since CalibrationFraction Remaining0Calibration 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. Sodium Fluoride F18 Injection USP emits radiation and must be handled with appropriate safety measures (2.1).Administer 300-450 MBq (8 to 12 mCi) as an intravenous injection in adults (2.4).Administer 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).Imaging can begin 1-2 hours after administration; optimally at one hour post administration (2.7).Encourage patients to void immediately prior to imaging the lumbar spine and bony pelvis (2.7).. Sodium Fluoride F18 Injection USP emits radiation and must be handled with appropriate safety measures (2.1).. Administer 300-450 MBq (8 to 12 mCi) as an intravenous injection in adults (2.4).. Administer 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).. Imaging can begin 1-2 hours after administration; optimally at one hour post administration (2.7).. Encourage patients to void immediately prior to imaging the lumbar spine and bony pelvis (2.7).. 2.1 Radiation Safety Drug Handling. Wear waterproof gloves and effective shielding when handling Sodium Fluoride 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 18 Injection USP.The dose of Sodium Fluoride 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 EOS, and measured by suitable radioactivity calibration system before administration [Description (11.2) ].. Wear waterproof gloves and effective shielding when handling Sodium Fluoride 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 18 Injection USP.. The dose of Sodium Fluoride 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 EOS, and measured by suitable radioactivity calibration system before administration [Description (11.2) ].. 2.2 Radiation Safety Patient Preparation. To 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 18 Injection USP.Encourage the patient to void one-half hour after administration of Sodium Fluoride 18 Injection USP and as frequently thereafter as possible for the next 12 hours. To 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 18 Injection USP.. Encourage the patient to void one-half hour after administration of Sodium Fluoride 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 18 Injection USP visually for particulate matter and discoloration before administration, whenever solution and container permit.Do not administer Sodium Fluoride 18 Injection USP containing particulate matter or discoloration; dispose of these unacceptable or unused preparations in safe manner, in compliance with applicable regulations.Aseptically withdraw Sodium Fluoride 18 Injection USP from its container. Calculate the necessary volume to administer based on calibration time and dose.. Inspect Sodium Fluoride 18 Injection USP visually for particulate matter and discoloration before administration, whenever solution and container permit.. Do not administer Sodium Fluoride 18 Injection USP containing particulate matter or discoloration; dispose of these unacceptable or unused preparations in safe manner, in compliance with applicable regulations.. Aseptically withdraw Sodium Fluoride 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 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 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 Does after Intravenous administration of Sodium Fluoride 18 InjectionOrganEstimated Radiation Dose mGy/MBqAdult70 kg [1]15 year56.8 kg [2]10 year33.2 kg [2]5 year19.8 kg [2]1 year9.7 kg [2]Adrenals0.00620.0120.0180.0280.052Brain0.0056N/AN/AN/AN/ABone surfaces0.0600.0500.0790.130.30Breast0.000280.00610.00970.0150.030GIGallbladder wall0.0044N/AN/AN/AN/AStomach wall0.00380.0080.0130.0190.036Small intestine0.00660.0120.0180.0280.052Upper large intestine wall0.00580.0100.0160.0260.046Lower large intestine wall0.00120.0160.0250.0370.063Heart 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 marrow0.0280.0530.0.880.180.38Skin0.0040N/AN/AN/AN/ASpleen 0.00420.00880.0140.0210.041Testes0.00780.0130.0210.0330.062Thymus0.0035N/AN/AN/AN/AThyroid0.00440.00840.0130.0200.036Urinary bladder wall0.250.270.40.611.1Uterus0.0190.0230.0370.0570.099Other tissueNA0.0100.0150.0240.044Effective Dose Equivalent (mSv/MBq)0.0270.0340.0520.0860.17[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 18 Injection USP can begin 1-2 hours after administration; optimally at hour post administration.Encourage the patient to void immediately prior to imaging the fluoride F18 radioactivity in the lumbar spine or bony pelvis.. Imaging of Sodium Fluoride 18 Injection USP can begin 1-2 hours after administration; optimally at hour post administration.. Encourage the patient to void immediately prior to imaging the fluoride F18 radioactivity in the lumbar spine or bony pelvis.

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 F18 in aqueous 0.9% sodium chloride solution. Sodium Fluoride 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) at EOS reference time of no-carrier-added sodium fluoride 18 in aqueous 0.9% sodium chloride solution (3). Sodium Fluoride 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 18 Injection USP with other drugs taken by patients undergoing PET imaging has not been studied.

HOW SUPPLIED SECTION.

16 HOW SUPPLIED/STORAGE AND HANDLING. Sodium Fluoride 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 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 shielding container of appropriate thickness. The product is available in 30 mL vial configuration with variable fill volume. The NDC number is:51760-002-30 (30 mL). StorageStore at 25C (77F); 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 18 Injection USP is indicated for diagnostic positron emission tomography (PET) imaging of bone to define areas of altered osteogenic activity.. Sodium Fluoride 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.

MECHANISM OF ACTION SECTION.

12.1 Mechanism of Action. Fluoride 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 18 Injection USP have not been performed.

NURSING MOTHERS SECTION.

8.3 Nursing Mothers. It is not known whether Sodium Fluoride 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 18 Injection USP or not to administer Sodium Fluoride 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.

Product Container Label. Container 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 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.

PHARMACODYNAMICS SECTION.

12.2 Pharmacodynamics. 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.

REFERENCES SECTION.

15 REFERENCES. 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.Radiation Dose to Patients from Radiopharmaceuticals,ICRP publication 53, Ann ICRP, 18 pages 15 and 74, 1987.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.. 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.. Radiation Dose to Patients from Radiopharmaceuticals,ICRP publication 53, Ann ICRP, 18 pages 15 and 74, 1987.. 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.

SPL UNCLASSIFIED SECTION.

2.1 Radiation Safety Drug Handling. Wear waterproof gloves and effective shielding when handling Sodium Fluoride 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 18 Injection USP.The dose of Sodium Fluoride 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 EOS, and measured by suitable radioactivity calibration system before administration [Description (11.2) ].. Wear waterproof gloves and effective shielding when handling Sodium Fluoride 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 18 Injection USP.. The dose of Sodium Fluoride 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 EOS, and measured by suitable radioactivity calibration system before administration [Description (11.2) ].

STORAGE AND HANDLING SECTION.

StorageStore at 25C (77F); excursions permitted to 15-30C (59-86F). Use the solution within 12 hours of the EOS reference time.

USE IN SPECIFIC POPULATIONS SECTION.

8 USE IN SPECIFIC POPULATIONS. Pregnancy: No human or animal data. Any radiopharmaceutical, including Sodium Fluoride F18 injection USP, may cause fetal harm. Use only if clearly needed (8.1) Nursing: decision should be made whether to interrupt nursing after Sodium Fluoride 18 Injection USP administration or not to administer Sodium Fluoride 18 Injection USP taking into consideration the importance of the drug to the mother.(8.3).Pediatrics: Children are more sensitive to radiation and may be at higher risk of cancer from Sodium Fluoride 18 injection USP (8.4).. Pregnancy: No human or animal data. Any radiopharmaceutical, including Sodium Fluoride F18 injection USP, may cause fetal harm. Use only if clearly needed (8.1) Nursing: decision should be made whether to interrupt nursing after Sodium Fluoride 18 Injection USP administration or not to administer Sodium Fluoride 18 Injection USP taking into consideration the importance of the drug to the mother.(8.3).. Pediatrics: Children are more sensitive to radiation and may be at higher risk of cancer from Sodium Fluoride 18 injection USP (8.4).. 8.1 Pregnancy. Pregnancy Category CAny radiopharmaceutical including Sodium Fluoride F18 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 reproduction studies have not been conducted with Sodium Fluoride 18 Injection USP. Prior to the administration of Sodium Fluoride 18 Injection USP to women of childbearing potential, assess for presence of pregnancy. Sodium Fluoride 18 Injection USP should be given to pregnant woman only if clearly needed.. 8.3 Nursing Mothers. It is not known whether Sodium Fluoride 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 18 Injection USP or not to administer Sodium Fluoride 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 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.

WARNINGS AND PRECAUTIONS SECTION.

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