NDC 73410-002 Sodium Fluoride F 18

Sodium Fluoride F 18

NDC Product Code 73410-002

NDC 73410-002-01

Package Description: 30 mL in 1 VIAL, MULTI-DOSE

NDC Product Information

Sodium Fluoride F 18 with NDC 73410-002 is a a human prescription drug product labeled by Decatur Memorial Hospital. The generic name of Sodium Fluoride F 18 is sodium fluoride f 18. The product's dosage form is injection and is administered via intravenous form.

Labeler Name: Decatur Memorial Hospital

Dosage Form: Injection - A sterile preparation intended for parenteral use; five distinct classes of injections exist as defined by the USP.

Product Type: Human Prescription Drug What kind of product is this?
Indicates the type of product, such as Human Prescription Drug or Human Over the Counter Drug. This data element matches the “Document Type” field of the Structured Product Listing.

Sodium Fluoride F 18 Active Ingredient(s)

What is the Active Ingredient(s) List?
This is the active ingredient list. Each ingredient name is the preferred term of the UNII code submitted.

  • SODIUM FLUORIDE F-18 10 mCi/mL

Inactive Ingredient(s)

About the Inactive Ingredient(s)
The inactive ingredients are all the component of a medicinal product OTHER than the active ingredient(s). The acronym "UNII" stands for “Unique Ingredient Identifier” and is used to identify each inactive ingredient present in a product.

  • SODIUM CHLORIDE (UNII: 451W47IQ8X)

Administration Route(s)

What are the Administration Route(s)?
The translation of the route code submitted by the firm, indicating route of administration.

  • Intravenous - Administration within or into a vein or veins.
  • Intravenous - Administration within or into a vein or veins.

Pharmacological Class(es)

What is a Pharmacological Class?
These are the reported pharmacological class categories corresponding to the SubstanceNames listed above.

  • Radioactive Diagnostic Agent - [EPC] (Established Pharmacologic Class)
  • Radiopharmaceutical Activity - [MoA] (Mechanism of Action)

Product Labeler Information

What is the Labeler Name?
Name of Company corresponding to the labeler code segment of the Product NDC.

Labeler Name: Decatur Memorial Hospital
Labeler Code: 73410
FDA Application Number: ANDA204464 What is the FDA Application Number?
This corresponds to the NDA, ANDA, or BLA number reported by the labeler for products which have the corresponding Marketing Category designated. If the designated Marketing Category is OTC Monograph Final or OTC Monograph Not Final, then the Application number will be the CFR citation corresponding to the appropriate Monograph (e.g. “part 341”). For unapproved drugs, this field will be null.

Marketing Category: ANDA - A product marketed under an approved Abbreviated New Drug Application. What is the Marketing Category?
Product types are broken down into several potential Marketing Categories, such as NDA/ANDA/BLA, OTC Monograph, or Unapproved Drug. One and only one Marketing Category may be chosen for a product, not all marketing categories are available to all product types. Currently, only final marketed product categories are included. The complete list of codes and translations can be found at www.fda.gov/edrls under Structured Product Labeling Resources.

Start Marketing Date: 11-06-2019 What is the Start Marketing Date?
This is the date that the labeler indicates was the start of its marketing of the drug product.

Listing Expiration Date: 12-31-2020 What is the Listing Expiration Date?
This is the date when the listing record will expire if not updated or certified by the product labeler.

Exclude Flag: N What is the NDC Exclude Flag?
This field indicates whether the product has been removed/excluded from the NDC Directory for failure to respond to FDA’s requests for correction to deficient or non-compliant submissions. Values = ‘Y’ or ‘N’.

* Please review the disclaimer below.

Sodium Fluoride F 18 Product Label Images

Sodium Fluoride F 18 Product Labeling Information

The product labeling information includes all published material associated to a drug. Product labeling documents include information like generic names, active ingredients, ingredient strength dosage, routes of administration, appearance, usage, warnings, inactive ingredients, etc.

Product Labeling Index

1 Indications And Usage

Sodium Fluoride F18 Injection, USP is indicated for diagnostic positron emission tomography (PET) imaging of bone to define areas of altered osteogenic activity.

2.1 Radiation Safety - Drug Handling

  • •Wear waterproof gloves and effective shielding when handling Sodium Fluoride F 18 Injection. 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. •The dose of Sodium Fluoride F 18 Injection 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 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.  •Encourage the patient to void one-half hour after administration of Sodium Fluoride F 18 Injection 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 visually for particulate matter and discoloration before administration, whenever solution and container permit.  •Do not administer Sodium Fluoride F 18 Injection 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 from its container.

Administer 300 MBq-450 MBq (8 mCi-12 mCi) as an intravenous injection.

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 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. Estimate Absorbed Radiation Doses After Administration of Sodium Fluoride F 18 Injection[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, 1987Organ Estimated Radiation Dose mGy/MBq Adult70 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 Surfaces0.0600.0500.0790.130.30Breasts0.00280.00610.00970.0150.030Gallbladder 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 Wall0.0120.0160.0250.00370.063Heart 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 TissuesN/A0.0100.0150.0240.044Effective DoseEquivalent mSv/MBq0.0270.0340.0520.0860.17

2.7 Imaging Guidelines

  • •Imaging of Sodium Fluoride F 18 Injection can begin 1–2 hours after administration; optimally at 1 hour post administration. •Encourage the patient to void immediately prior to imaging the fluoride F18 radioactivity in the lumbar spine or bony pelvis.

3 Dosage Forms And Strengths

Multiple-dose vial containing 370 MBq/mL-7,400 MBq/mL (10 mCi/mL-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 is a clear, colorless, sterile, pyrogen-free and preservative-free solution for intravenous administration.

4 Contraindications

None.

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 may increase the risk of cancer. Carcinogenic and mutagenic studies with Sodium Fluoride F 18 Injection 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 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 with other drugs taken by patients undergoing PET imaging has not been studied.

8.1 Pregnancy

Pregnancy Category CAny 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 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.

8.3 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 Injection 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.

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 370 MBq to 7,400 MBq (10 mCi-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 (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 Radiation Emission Data for Fluorine F 18 Injection* Produced by positron annihilation[3] Kocher, D.C. Radioactive Decay Tables DOE/TIC-I 1026, 89 (1981)Radiation/Emission% Per DisintegrationMean EnergyPositron(β+)96.73249.8 keVGamma (±)*193.46511.0 keVThe specific gamma ray constant (point source air kerma coefficient) for fluorine 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 mm lead (Pb). The range of attenuation coefficients for this radionuclide as a function of lead shield thickness 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) shieldingShield thickness (Pb) mmCoefficient of Attenuation00.0040.5080.25130.10260.01390.001520.0001Table 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 Fluorine F 18* calibration timeTime Since CalibrationFraction Remaining0*1.0015 minutes0.90930 minutes0.82660 minutes0.683110 minutes0.500220 minutes0.250440 minutes0.06012 hours0.01124 hours0.0001

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 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.

13.1 Carcinogenesis, Mutagenesis, Impairment Of Fertility

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

14.1 Metastatic Bone Disease

The doses used in reported studies ranged from 2.7 mCi-20 mCi (100 MBq-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 to15 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, 19873.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

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 MBq/mL and 7,400 MBq/mL (10 mCi/mL - 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:73410-002-01 (30 mL)StorageStore 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.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.

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.

* Please review the disclaimer below.