Flortaucipir F18
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Alara Ece Dagsali, M.D.
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Overview
Flortaucipir F18 is {{{aOrAn}}} specifically bind to misfolded tau proteins in the brain that is FDA approved for the treatment of TAUVID is indicated for use with positron emission tomography (PET) imaging of the brain to estimate the density and distribution of aggregated tau neurofibrillary tangles (NFTs) in adult patients with cognitive impairment who are being evaluated for Alzheimer's disease (AD).
Limitations of Use
TAUVID is not indicated for use in the evaluation of patients for chronic traumatic encephalopathy (CTE). Common adverse reactions include *Headache
- Injection site pain
- Increased blood pressure.
Adult Indications and Dosage
FDA-Labeled Indications and Dosage (Adult)
TAUVID is indicated for use with positron emission tomography (PET) imaging of the brain to estimate the density and distribution of aggregated tau neurofibrillary tangles (NFTs) in adult patients with cognitive impairment who are being evaluated for Alzheimer's disease (AD).
Limitations of Use
TAUVID is not indicated for use in the evaluation of patients for chronic traumatic encephalopathy (CTE)
DOSAGE The recommended amount of radioactivity to be administered for PET imaging is 370 MBq (10 mCi), administered as an intravenous bolus injection in a total volume of 10 mL or less.
Off-Label Use and Dosage (Adult)
Guideline-Supported Use
There is limited information regarding Off-Label Guideline-Supported Use of Flortaucipir F18 in adult patients.
Non–Guideline-Supported Use
There is limited information regarding Off-Label Non–Guideline-Supported Use of Flortaucipir F18 in adult patients.
Pediatric Indications and Dosage
FDA-Labeled Indications and Dosage (Pediatric)
There is limited information regarding Flortaucipir F18 FDA-Labeled Indications and Dosage (Pediatric) in the drug label.
Off-Label Use and Dosage (Pediatric)
Guideline-Supported Use
There is limited information regarding Off-Label Guideline-Supported Use of Flortaucipir F18 in pediatric patients.
Non–Guideline-Supported Use
There is limited information regarding Off-Label Non–Guideline-Supported Use of Flortaucipir F18 in pediatric patients.
Contraindications
None
Warnings
Risk of Misdiagnosis in Patients Evaluated for Alzheimer's disease
TAUVID does not target β-amyloid, one of two required components of the neuropathological diagnosis of AD.
TAUVID performance for detecting tau pathology was assessed in terminally ill patients, the majority of whom had AD dementia with B3 level NFT pathology. TAUVID performance for detecting tau pathology may be lower in patients in earlier stages of the pathological spectrum.
Negative TAUVID Scan
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 TAUVID scan. Consider additional evaluation to confirm the absence of AD pathology in patients with a negative TAUVID scan.
False Positive TAUVID Scan
Small foci of noncontiguous tracer uptake may lead to a false positive TAUVID scan. Only uptake of tracer in the neocortex should contribute to the interpretation of a positive TAUVID scan.
Risk of Chronic Traumatic Encephalopathy Misdiagnosis The safety and effectiveness of TAUVID have not been established for patients being evaluated for CTE. Preliminary non-clinical and clinical investigations suggest differences in tau conformation and distribution may limit flortaucipir F 18 binding. Therefore, TAUVID is not indicated for detection of CTE.
Radiation Risk Diagnostic radiopharmaceuticals, including TAUVID, expose patients to radiation. Radiation exposure is associated with a dose-dependent increased risk of cancer. Ensure safe handling and preparation procedures to protect patients and health care workers from unintentional radiation exposure
Adverse Reactions
Clinical Trials Experience
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.
In clinical studies, 1,921 study participants were exposed to TAUVID. In these studies, 885 study participants received 240 MBq of TAUVID (about 65% of the recommended dose) and 1,036 study participants received 370 MBq of TAUVID (the recommended dose).
Adverse reactions with a frequency <0.5% in adults who received TAUVID in clinical trials include:
Nervous system disorders: dysgeusia
Postmarketing Experience
There is limited information regarding Flortaucipir F18 Postmarketing Experience in the drug label.
Drug Interactions
There is limited information regarding Flortaucipir F18 Drug Interactions in the drug label.
Use in Specific Populations
Pregnancy
Pregnancy Category (FDA):
There is no FDA guidance on usage of Flortaucipir F18 in women who are pregnant.
Pregnancy Category (AUS):
There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Flortaucipir F18 in women who are pregnant.
Labor and Delivery
All radiopharmaceuticals, including TAUVID, have the potential to cause fetal harm depending on the fetal stage of development and the magnitude of radiation dose. Advise a pregnant woman of the potential risks of fetal exposure to radiation doses with administration of TAUVID. TAUVID is not likely to be used in females of reproductive age.
There are no available data on TAUVID use in pregnant women. No animal reproduction studies using flortaucipir F 18 have been conducted to evaluate its effect on female reproduction and embryo-fetal development.
The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively.
Nursing Mothers
There are no data on the presence of flortaucipir F 18 in human milk, or its effects on the breastfed infant or milk production. Lactation studies have not been conducted in animals. Advise a lactating woman to avoid breastfeeding for 4 hours after TAUVID administration in order to minimize radiation exposure to a breastfed infant.
Pediatric Use
The safety and effectiveness of TAUVID in pediatric patients have not been established.
Geriatic Use
Of 1,921 study participants in completed clinical studies of TAUVID, 1,544 (80%) TAUVID-treated subjects were ≥ 65 years old, while 839 (44%) were ≥ 75 years old. No overall differences in safety or effectiveness of TAUVID were observed between subjects ≥ 65 years old and younger adult subjects, and other reported clinical experience has not identified differences in safety or effectiveness between elderly and younger patients.
Gender
There is no FDA guidance on the use of Flortaucipir F18 with respect to specific gender populations.
Race
There is no FDA guidance on the use of Flortaucipir F18 with respect to specific racial populations.
Renal Impairment
There is no FDA guidance on the use of Flortaucipir F18 in patients with renal impairment.
Hepatic Impairment
There is no FDA guidance on the use of Flortaucipir F18 in patients with hepatic impairment.
Females of Reproductive Potential and Males
There is no FDA guidance on the use of Flortaucipir F18 in women of reproductive potentials and males.
Immunocompromised Patients
There is no FDA guidance one the use of Flortaucipir F18 in patients who are immunocompromised.
Administration and Monitoring
Administration
- Assessment of pregnancy status is recommended in females of reproductive potential before administering TAUVID.
- Use aseptic technique and radiation shielding during the preparation and administration of TAUVID.
- Visually inspect the radiopharmaceutical solution prior to administration. Do not use it if it contains particulate matter or if it is discolored (TAUVID is a clear, colorless solution).
- TAUVID may be diluted aseptically with 0.9% Sodium Chloride Injection to a maximum dilution of 1:5 by the end-user. Diluted product should be used within 4 hours of dilution and prior to product expiry.
- Assay the dose in a suitable dose calibrator prior to administration.
Monitoring
There is limited information regarding Flortaucipir F18 Monitoring in the drug label.
IV Compatibility
There is limited information regarding the compatibility of Flortaucipir F18 and IV administrations.
Overdosage
There is limited information regarding Flortaucipir F18 overdosage. If you suspect drug poisoning or overdose, please contact the National Poison Help hotline (1-800-222-1222) immediately.
Pharmacology
There is limited information regarding Flortaucipir F18 Pharmacology in the drug label.
Mechanism of Action
Flortaucipir F 18 binds to aggregated tau protein. In the brains of patients with AD, tau aggregates combine to form NFTs, one of two components required for the neuropathological diagnosis of AD. In vitro, flortaucipir F 18 binds to paired helical filament (PHF) tau purified from brain homogenates of donors with AD. The dissociation constant (Kd) of flortaucipir F 18 binding to PHFs is 0.57 nM. In vivo, flortaucipir F 18 is differentially retained in neocortical areas that contain aggregated tau. In vitro, tritiated flortaucipir has been reported to bind with low nanomolar affinity to monoamine oxidase-A and monoamine oxidase-B, which could contribute to off target binding.
Structure
There is limited information regarding Flortaucipir F18 Structure in the drug label.
Pharmacodynamics
The relationship between flortaucipir F 18 plasma concentrations and image interpretation was not explored in clinical trials.
Effect of MAO Inhibitors on Flortaucipir Binding in AD Patients
TAUVID PET signal was slightly reduced by rasagiline, a MAO-B inhibitor, in vivo in low tau, high MAO-B areas of the brain such as the nucleus accumbens, putamen, and caudate. However, there is little potential for MAO binding to affect TAUVID scan interpretation in neocortical areas.
Pharmacokinetics
After intravenous administration of TAUVID, flortaucipir F 18 was distributed throughout the body with less than 10% of the injected F 18 radioactivity present in the blood by 5 minutes following administration, and less than 5% present in the blood by 10 minutes after administration. The residual F 18 in circulation during the 80-minute to 100-minute imaging window was approximately 28% to 34% parent, with the remainder being metabolites.
Clearance occurs primarily by hepatobiliary and renal excretion.
Nonclinical Toxicology
Animal studies to assess the carcinogenicity or reproductive toxicity potentials of flortaucipir F 18 have not been conducted.
In an in vitro bacterial reverse mutation assay (Ames test), increases in the number of revertant colonies were observed in 4 of the 5 strains exposed to flortaucipir F 19. In a chromosomal aberration in vitro study with Chinese hamster ovary (CHO) cells, flortaucipir F 19 increased the percent of cells with structural aberrations with 3 hour exposure with or without S9 metabolic activation. Twenty hour exposure without activation produced an increase in structural aberrations at all tested concentrations.
Flortaucipir F 19 was evaluated in a rat micronucleus study and showed no genotoxicity. In this study, flortaucipir F 19 did not increase the number of micronucleated polychromatic erythrocytes at the highest achievable dose level, 1600 μg/kg/day, when given for two consecutive days.
Clinical Studies
The performance of TAUVID imaging to estimate the density and distribution of aggregated tau neurofibrillary tangles (NFTs) was evaluated in two clinical studies: Study 1 (NCT02516046) and Study 2 (NCT03901092). In each study, TAUVID imaging was interpreted by 5 independent readers who were blinded to clinical information. Readers interpreted TAUVID imaging as positive or negative.
Study 1 enrolled 156 terminally ill patients who agreed to undergo TAUVID imaging and to participate in a postmortem brain donation program. In 64 of these patients, reader interpretation of the TAUVID scan was compared to tau pathology based on scoring provided by independent pathologists, who evaluated the density and distribution of NFTs in the post-mortem brain. Of the 64 patients, the mean age was 83 years (range 55 to 100); 34 were female; 49 had dementia, 1 had mild cognitive impairment, and 14 had no cognitive impairment on clinical evaluation around the time of TAUVID imaging.
The performance of the five TAUVID readers for sensitivity (95% CI) ranged from 92% (80, 97) to 100% (91, 100) and for specificity (95% CI) ranged from 52% (34, 70) to 92% (75, 98). Exploratory analysis evaluated how the same TAUVID interpretations distinguished B2-B3 from B0-B1 tau pathology, a threshold used in integrating tau and amyloid pathology for the neuropathological diagnosis of AD. In this analysis, the performance of the five TAUVID readers for sensitivity (95% CI) ranged from 68% (55, 79) to 86% (74, 93) and for specificity (95% CI) ranged from 63% (31, 86) to 100% (68, 100).
Study 2 included the same terminally ill patients as in Study 1 (plus 18 additional terminally ill patients) and 159 patients with cognitive impairment being evaluated for AD (the indicated population). Inter-reader agreement for five new TAUVID readers was evaluated using Fleiss' kappa statistic (95% CI) and found to be 0.87 (0.83, 0.91) across all 241 patients. Exploratory analysis evaluated inter-reader agreement in two subgroups. In this analysis, Fleiss' kappa (95% CI) was 0.82 (0.75, 0.88) in the terminally ill patients and 0.90 (0.85, 0.95) in the indicated population.
How Supplied
TAUVID injection is supplied in a 50 mL or 100 mL multiple-dose vial containing a clear, colorless solution free of visible particulate matter at a strength of 300 MBq/mL to 3,700 MBq/mL (8.1 mCi/mL to 100 mCi/mL) flortaucipir F 18 at end of synthesis. Each vial contains multiple doses and is enclosed in a shield container to minimize external radiation exposure.
Storage
Store TAUVID at 25°C (77°F); excursions permitted to 15°C to 30°C (59°F to 86°F). TAUVID does not contain a preservative. Store TAUVID upright in a shielding container. The expiration date and time are provided on the container label. Use TAUVID within the labeled expiration.
Images
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Patient Counseling Information
Radiation Risk
Advise patients of the radiation risk of TAUVID.
Pregnancy
Advise a pregnant woman of the potential risks of fetal exposure to radiation doses with TAUVID.
Lactation
Advise a lactating woman to avoid breastfeeding for 4 hours after TAUVID administration in order to minimize radiation exposure to a breastfed infant.
Precautions with Alcohol
Alcohol-Flortaucipir F18 interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.
Brand Names
Tauvid
Look-Alike Drug Names
There is limited information regarding Flortaucipir F18 Look-Alike Drug Names in the drug label.
Price
References
The contents of this FDA label are provided by the National Library of Medicine.