Sodium Fluoride

University of Texas MD Anderson Cancer Center

HIGHLIGHTS OF PRESCRIBING INFORMATIONThese highlights do not include all the information needed to use Sodium Fluoride F 18 Injection safely and effectively. See full prescribing information for Sodium Fluoride F 18 Injection. SODIUM FLUORIDE F 18 INJECTIONFor Intravenous UseInitial U.S. Approval: DOSAGE FORMS AND STRENGTHSMultiple-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(3). Sodium Fluoride F 18 Injection is a clear, colorless, sterile, pyrogen-free and preservative-free solution for intravenous administration.Side EffectsNo adverse reactions have been reported for Sodium Fluoride F 18 Injection based on a review of the published literature, publicly available reference sources, and adverse drug reaction reporting systems. To report SUSPECTED ADVERSE REACTIONS, contact UTMDACC at 1-713-563-5455 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. USE IN SPECIFIC POPULATIONS Pregnancy: No human or animal data. Any radiopharmaceutical, including Sodium Fluoride F 18 Injection, may cause fetal harm. Use only if clearly needed(8.1) Nursing: A decision should be made whether to interrupt nursing after Sodium Fluoride F 18 Injection administration or not to administer Sodium Fluoride F 18 Injection taking into consideration the importance of the drug to the mother(8.2) Pediatrics: Children are more sensitive to radiation and may be held at higher risk of cancer from Sodium Fluoride F 18 Injection(8.4).

FULL PRESCRIBING INFORMATION: CONTENTS*

• 3 DOSAGE FORMS AND STRENGTHS
• 6 SODIUM FLUORIDE ADVERSE REACTIONS
• 11 SODIUM FLUORIDE DESCRIPTION
  • 11.1 Chemical Characteristics
  • 11.2 Physical Characteristics
• 16 HOW SUPPLIED
  • Storage
  • Handling
• FINAL PRODUCT VIAL LABEL - 30 mL VIAL
• 8  USE IN SPECIFIC POPULATIONS
  • 8.1  Pregnancy
  • 8.2  Nursing Mothers
  • 8.4 Pediatric Use

FULL PRESCRIBING INFORMATION

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 F 18 Injection is a clear, colorless, sterile, pyrogen-free and preservative-free solution for intravenous administration.

6 ADVERSE REACTIONS

No adverse reactions have been reported for Sodium Fluoride F 18 Injection 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.

11 DESCRIPTION

11.1 Chemical Characteristics

Sodium Fluoride F 18 Injection is a positron emitting radiopharmaceutical, containing no-carrier-added, radioactive fluoride F18 that is used for diagnostic purposes in conjunction with PET imaging. It is administered by intravenous injection. The active ingredient, sodium fluoride F18, 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 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 F18, 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 F18 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 F18 atom decays to stable ¹⁸O-oxygen.

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%.

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.

16 HOW SUPPLIED

Sodium Fluoride F 18 Injection is supplied in a multiple-dose Type I glass vial with (elastomeric) stopper and aluminum crimp seal containing between 370-7,400 MBq/mL (10 to 200 mCi/mL) of no-carrier-added sodium fluoride F18, 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:

60215-412-10 (10 mL)

Storage

Store at 20°C to 25°C (68°F to 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.

Manufactured and Distributed by:

University of Texas MD Anderson Cancer Center 

Center for Advanced Biomedical Imaging

Cyclotron Radiochemistry Facility

1881 East Road

Houston, TX  77054

FINAL PRODUCT VIAL LABEL - 30 mL VIAL

8  USE IN SPECIFIC POPULATIONS

Pregnancy Category C

8.1  Pregnancy

Any radiopharmaceutical including Sodium Fluoride F 18 Injection 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 and toxicity studies have not been conducted with Sodium Fluoride F 18 Injection.  Prior to the administration of Sodium Fluoride F 18 Injection to women of childbearing potential, assess for presence of pregnancy.  Sodium Fluoride F 18 Injection should be given to a pregnant woman only if clearly needed.

8.2  Nursing Mothers

It is not known whether Sodium Fluoride F 18 Injection 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 or not to administer Sodium Fluoride F 18 Injection, 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.

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