Sodium Fluoride F 18 (Page 3 of 3)

12 CLINICAL PHARMACOLOGY

12.1 Mechanism of Action

Fluoride F18 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 F18 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 F18 that is delivered to bone by the blood is retained in the bone. One hour after administration of fluoride F18 only about 10% of the injected dose remains in the blood. Fluoride F18 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 F18 in bone appears to be primarily a function of blood flow to the bone and the efficiency of the bone in extracting the fluoride F18. Fluoride F18 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 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 (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, focally increased tracer uptake is seen in both osteolytic and osteoblastic bone lesions. Negative PET imaging results with Sodium Fluoride F 18 Injection do not preclude the diagnosis of bone metastases. Also, as benign bone lesions are also detected by Sodium Fluoride F 18 Injection, 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 (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).

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 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 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 shielded container of appropriate thickness.

The product is available in a 30 mL vial configuration with a variable fill volume. The NDC number is:
60055-623-30 (30 mL)

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.

Manufactured and Distributed by:

Jubilant Radiopharma
Yardley, PA 19067

Drug Product Label

SODIUM FLUORIDE F 18 sodium fluoride f 18 injection, solution

Product Information Product Type HUMAN PRESCRIPTION DRUG Item Code (Source) NDC:60055-623 Route of Administration INTRAVENOUS DEA Schedule

Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength SODIUM FLUORIDE F-18 (FLUORIDE ION F-18) FLUORIDE ION F-18 200 mCi in 1 mL

Inactive Ingredients Ingredient Name Strength SODIUM CHLORIDE 9 mg in 1 mL

Packaging # Item Code Package Description Multilevel Packaging 1 NDC:60055-623-30 30 mL in 1 VIAL None

Marketing Information Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date ANDA ANDA203968 01/26/2011

Labeler — JUBILANT DRAX IMAGE RADIOPHARMACIES, INC. DBA JUBILANT RADIOPHARMA (118310678)

Registrant — JUBILANT DRAX IMAGE RADIOPHARMACIES, INC. DBA JUBILANT RADIOPHARMA (118310678)

Establishment
Name	Address	ID/FEI	Operations
JUBILANT DRAX IMAGE RADIOPHARMACIES, INC. DBA JUBILANT RADIOPHARMA		080871701	POSITRON EMISSION TOMOGRAPHY DRUG PRODUCTION (60055-623)

Establishment
Name	Address	ID/FEI	Operations
JUBILANT DRAX IMAGE RADIOPHARMACIES, INC. DBA JUBILANT RADIOPHARMA		080871737	positron emission tomography drug production (60055-623)

Revised: 02/2022 JUBILANT DRAX IMAGE RADIOPHARMACIES, INC. DBA JUBILANT RADIOPHARMA