Flortaucipir F 18 is a parenteral radioactive diagnostic agent indicated for positron emission tomography (PET) imaging of the brain to estimate the density and distribution of aggregated tau neurofibrillary tangles (NFTs) in patients with cognitive impairment who are being evaluated for Alzheimer's disease (AD). NFTs are 1 of 2 required components of the neuropathological diagnosis of AD; flortaucipir F 18 does not target beta-amyloid neuritic plaque. A positive scan supports the presence of widely distributed tau neuropathology (B3 tau pathology), with increased neocortical activity in posterolateral temporal, occipital, or parietal/precuneus region(s), with or without frontal activity. The safety and effectiveness of flortaucipir F 18 have not been established in patients being evaluated for chronic traumatic encephalopathy (CTE). Data suggest differences in tau conformation and distribution may limit flortaucipir F 18 binding. Therefore, flortaucipir F 18 is not indicated for detection of CTE.
General Administration Information
For storage information, see the specific product information within the How Supplied section.
NOTE: Flortaucipir F 18 is a radioactive material. To ensure minimum radiation exposure to occupational workers and to minimize radiation exposure to patients, observe appropriate precautions that are consistent with proper patient management. Radiopharmaceuticals should only be used by nuclear physicians or radiopharmacists who are qualified by training and experience in the safe use and handling of radioactive material, and whose experience and training have been approved by the appropriate governmental agency authorized to license the use of radiopharmaceuticals.
NOTE: Storage and disposal should be controlled in compliance with appropriate regulations of the governmental agency authorized to license the use of radiopharmaceuticals.
Route-Specific Administration
Injectable Administration
-To minimize radiation exposure, maintain adequate shielding, including lead-glass syringe shields, during the life of the product. Vials are enclosed in an appropriate radiation shield.
-Use waterproof gloves when handling and administering flortaucipir F 18.
-Visually inspect parenteral products for particulate matter and discoloration. The solution is clear and colorless; discard if the vial contains particulate matter or if the solution is discolored.
Intravenous Administration
-Using aseptic technique and radiation shielding, withdraw the appropriate volume.
-The dose may be diluted with 0.9% Sodium Chloride Injection to a maximum dilution of 1:5. Do not exceed a total dose volume of 10 mL.
-Assay the dose in a suitable dose calibrator.
-Administer by IV bolus injection. Follow the flortaucipir F 18 injection with an intravenous flush of 0.9% Sodium Chloride Injection.
-Initiate a 20-minute positron emission tomography (PET) scan approximately 80 minutes after drug administration. With the patient supine, position the head to center the brain (including the cerebellum) in the PET scanner field of view. Tape or other flexible head restraints may be used to reduce head movement.
-Storage: Use diluted product within 3 hours of dilution and before product expiry.
Headache (1.4%), injection site reaction (i.e., injection site pain, 1.2%), and increased blood pressure (0.8%) were reported in flortaucipir F 18-treated subjects in clinical trials.
Dysgeusia (less than 0.5%) was reported in flortaucipir F 18-treated subjects in clinical trials.
Interpret flortaucipir F 18 imaging independently of the patient's clinical features and other imaging.
Flortaucipir F 18 does not target beta-amyloid, 1 of 2 required components of the neuropathological diagnosis of Alzheimer's disease (AD). Flortaucipir F 18 performance for detecting tau pathology was established in terminally ill patients, most of whom had AD dementia with B3 level neurofibrillary tangles (NFTs) pathology; flortaucipir F 18 performance for detecting tau pathology may be lower in patients at earlier stages of the pathological spectrum. NFTs may be present at levels that qualify for the neuropathological diagnosis of AD (B2 tau pathology in the presence of at least moderate levels of cortical amyloid pathology) in patients with a negative flortaucipir F 18 scan. Consider additional evaluation to confirm the absence of AD pathology in patients with a negative flortaucipir F 18 scan. Also, small foci of noncontiguous tracer uptake may lead to a false-positive flortaucipir F 18 scan. Interpret scans that have isolated or noncontiguous, small foci in any region with caution. Only consider uptake of tracer in the neocortex in the interpretation of a positive flortaucipir F 18 scan. For cases where there is uncertainty as to the location of neocortical uptake, use co-registered anatomical imaging to improve localization of uptake.
The safety and effectiveness of flortaucipir F 18 have not been established in patients being evaluated for chronic traumatic encephalopathy (CTE). Data suggest differences in tau conformation and distribution may limit flortaucipir F 18 binding. Therefore, flortaucipir F 18 is not indicated for detection of CTE.
Flortaucipir F 18 should be used only by nuclear physicians or radiopharmacists who are qualified by training and experience in the safe use and handling of radioactive materials, and whose experience and training have been approved by the appropriate governmental agency authorized to license the use of radiopharmaceuticals. Care should be taken to assure minimum accidental exposure of radiation to occupational workers, including the use of waterproof gloves and effective shielding. Furthermore, take care to minimize radiation exposure to the patient by proper patient management before, during, and after the procedure.
There are no available data on flortaucipir F 18 use in pregnant women. No animal reproduction studies using flortaucipir F 18 have been conducted to evaluate its effect on female reproduction and embryofetal development. All radiopharmaceuticals, including flortaucipir F 18, have the potential to cause fetal harm depending on the stage of fetal development and the magnitude of the radiopharmaceutical dose. Flortaucipir F 18 is unlikely to be used in females of reproductive age. If considering flortaucipir F 18 administration to a pregnant woman, inform the patient about the potential for adverse pregnancy outcomes based on the radiation dose from the drug and the gestational timing of exposure.
There are no data on the presence of flortaucipir F 18 in human milk or its effects on the breast-fed infant or milk production. Lactation studies have not been conducted in animals. To decrease radiation exposure to the breast-fed infant, advise a lactating woman to avoid breast-feeding for 4 hours after administration of flortaucipir F 18.
Flortaucipir F 18 may be associated with reproductive risk. Assess the pregnancy status of any female of reproductive potential by pregnancy testing before administering flortaucipir F 18.
For use with positron emission tomography (PET) imaging of the brain to estimate the density and distribution of aggregated tau neurofibrillary tangles in patients with cognitive impairment who are being evaluated for Alzheimer's Disease:
NOTE: Dosage measured in megabecquerels (MBq) and millicuries (mCi).
Intravenous dosage:
Adults: 370 MBq (10 mCi) IV as single dose. Begin a 20-minute PET image starting approximately 80 minutes after administration.
Maximum Dosage Limits:
-Adults
370 MBq (10 mCi) IV per procedure.
-Geriatric
370 MBq (10 mCi) IV per procedure.
-Adolescents
Safety and efficacy have not been established.
-Children
Safety and efficacy have not been established.
-Infants
Safety and efficacy have not been established.
-Neonates
Safety and efficacy have not been established.
Patients with Hepatic Impairment Dosing
Specific guidelines for dosage adjustments in hepatic impairment are not available; it appears that no dosage adjustments are needed.
Patients with Renal Impairment Dosing
Specific guidelines for dosage adjustments in renal impairment are not available; it appears that no dosage adjustments are needed.
*non-FDA-approved indication
There are no drug interactions associated with Flortaucipir F 18 products.
Flortaucipir F 18 is a radiolabeled diagnostic agent. Flortaucipir F 18 binds to aggregated tau protein; it is differentially retained in neocortical areas that contain aggregated tau. In the brain of patients with Alzheimer's Disease (AD), tau aggregates combine to form neurofibrillary tangles (NFTs), 1 of 2 components required for neuropathological diagnosis of AD. Flortaucipir F 18 does not target beta-amyloid. The F 18 isotope produces a positron signal that can be detected by a positron emission tomography (PET) scanner. Interpretation of the flortaucipir F 18 PET scan is based on the pattern and density of the radioactive signal within the neocortical gray matter (not within the white matter or in regions outside the brain). A positive scan shows increased neocortical activity in posterolateral temporal, occipital, or parietal/precuneus region(s), with or without frontal activity. A positive scan supports the presence of widely distributed tau neuropathology (B3 tau pathology). A negative scan shows no increased neocortical activity or shows increased neocortical activity isolated to the mesial temporal, anterolateral temporal, or frontal regions.
Flortaucipir F 18 performance for detecting tau pathology was established in terminally ill patients, most of whom had AD dementia with B3 level NFTs pathology; flortaucipir F 18 performance for detecting tau pathology may be lower in patients at earlier stages of the pathological spectrum. NFTs may be present at levels that qualify for the neuropathological diagnosis of AD (B2 tau pathology in the presence of at least moderate levels of cortical amyloid pathology) in patients with a negative flortaucipir F 18 scan. Consider additional evaluation to confirm the absence of AD pathology in patients with a negative flortaucipir F 18 scan. Also, small foci of noncontiguous tracer uptake may lead to a false-positive flortaucipir F 18 scan. Interpret scans that have isolated or noncontiguous, small foci in any region with caution. Only consider uptake of tracer in the neocortex in the interpretation of a positive flortaucipir F 18 scan. For cases where there is uncertainty as to the location of neocortical uptake, use co-registered anatomical imaging to improve localization of uptake.
The safety and effectiveness of flortaucipir F 18 have not been established in patients being evaluated for chronic traumatic encephalopathy (CTE). Data suggest differences in tau conformation and distribution may limit flortaucipir F 18 binding. Therefore, flortaucipir F 18 is not indicated for detection of CTE.
Flortaucipir F 18 is administered intravenously. After intravenous administration, flortaucipir F 18 distributes throughout the body with less than 10% of the injected F 18 radioactivity present in the blood by 5 minutes after administration, and less than 5% present by 10 minutes. The residual F 18 in circulation during the 80- to 100-minute imaging window is approximately 28% to 34% parent drug, with the remainder being metabolites. Clearance occurs primarily by hepatobiliary and renal excretion.
Affected cytochrome P450 isoenzymes and drug transporters: none
-Route-Specific Pharmacokinetics
Intravenous Route
The amount of radiation absorbed after exposure to a 370 MBq (10 mCi) dose of flortaucipir F 18 is estimated to be 8.7 mSv. A positron emission tomography (PET) or computerized tomography (CT) scan will increase radiation exposure by an amount dependent on the settings used. The physical half-life of flortaucipir F 18 is 109.8 minutes.