These Highlights Do Not Include All The Information Needed To Use Tauvid Safely And Effectively. See Full Prescribing Information For Tauvid.

Limitations of Use

TAUVID is not indicated for use in the evaluation of patients for chronic traumatic encephalopathy (CTE) [see Warnings and Precautions (5.2)].

PACKAGE LABEL – Tauvid 100 mci 50 mL SHIELD

NDC 0002-1220-50

Tauvid™

Flortaucipir F 18 Injection

50 mL Multiple-Dose Vial

Sterile

Rx Only

CAUTION ☢ RADIOACTIVE MATERIAL

300 MBq/mL to 3,700 MBq/mL (8.1 mCi/mL to 100 mCi/mL) at End of Synthesis

For Intravenous Use Only

_____MBq (_____mCi) in _____mL at _____:_____ on _____

Expires at _____:_____ on _____

Batch No._____

Dosage: See prescribing information.

Contains up to 2 micrograms of flortaucipir, 1.5 mg L-cysteine hydrochloride monohydrate USP, 2.1 mg of dibasic sodium phosphate anhydrous USP, up to 55 micrograms of hydrogen chloride and 0.1 mL dehydrated alcohol USP in 0.9% sodium chloride injection USP per milliliter of solution. Store vial upright in a shielding container at 25°C (77°F); excursions permitted to 15°C to 30°C (59°F to 86°F).

Manufactured by PETNET Solutions, Inc. Knoxville, TN 37932 for Avid Radiopharmaceuticals, a wholly-owned subsidiary of Eli Lilly and Company, Philadelphia, PA 19104

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.

The goal of the read is to identify and locate areas of flortaucipir activity in the neocortex that are greater than the background activity (background activity is defined as up to 1.65-fold the measured cerebellar average). For optimal display, select a color scale with a rapid transition between two distinct colors and adjust the scale so that the transition occurs at the 1.65-fold threshold. Examine the posterolateral temporal (PLT), occipital, parietal, and frontal regions bilaterally. Neocortical activity in either hemisphere contributes to image interpretation. Activity in white matter or regions outside the brain does not contribute to image interpretation. To help identify the PLT, consider subdividing the temporal lobe into four quadrants as instructed below. Activity in the anterior and medial temporal lobe does not contribute to image interpretation of a positive TAUVID pattern.

The safety and effectiveness of TAUVID in pediatric patients have not been established.

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.

Diagnostic radiopharmaceuticals, including TAUVID, expose patients to radiation [see Dosage and Administration (2.7)]. 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 [see Dosage and Administration (2.1, 2.2)].

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 [see Dosage and Administration (2.6)].

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 (see Table 5). 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.

Image reader performance for distinguishing B3 (positive) from B0-B2 (negative) tau pathology is shown in Table 6.

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) [see Warnings and Precautions (5.1)].

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.

None.

Most common adverse reactions (frequency ≥ 0.5%) were headache, injection site pain, and increased blood pressure. (6.1)

To report SUSPECTED ADVERSE REACTIONS, contact Eli Lilly and Company at 1-800-LillyRx (1-800-545-5979) or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

The relationship between flortaucipir F 18 plasma concentrations and image interpretation was not explored in clinical trials.

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.

Starting approximately 80 minutes after the TAUVID intravenous injection, obtain a 20-minute PET image 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.

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).

The point source air-kerma coefficient for F18 is 3.74E^-17 Gy m²/(Bq s). The first half-value thickness of lead (Pb) for F 18 gamma rays is approximately 6 mm. The relative reduction of radiation emitted by F 18 that results from various thicknesses of lead shielding is shown in Table 4. The use of 8 cm of Pb will decrease the radiation transmission (i.e., exposure) by a factor of about 10,000.

Radiation absorbed dose estimates are shown in Table 1 for organs and tissues of adults from intravenous administration of TAUVID. The effective radiation dose resulting from administration of 370 MBq (10 mCi) of TAUVID to an adult weighing 70 kg is estimated to be 8.7 mSv. Critical organs include the upper large intestinal wall, small intestine, and liver. When PET/CT is performed, exposure to radiation will increase in an amount dependent on the settings used in the CT acquisition.

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.

Interpret TAUVID imaging independently of the patient's clinical features and other imaging.

Interpret the PET TAUVID images based upon the pattern and density of the radioactive signal within the neocortical gray matter (not within white matter or in regions outside of the brain). Only uptake of tracer in the neocortical grey matter regions should contribute to scan interpretation.

Off-target binding may be seen in the choroid plexus, striatum, and brainstem nuclei. Small foci of noncontiguous tracer uptake may lead to false positive interpretation. Interpret scans that have isolated or noncontiguous, small foci in any region with caution. Some scans may be difficult to interpret due to image noise or motion artifact. For cases where there is uncertainty as to the location of neocortical uptake, use co-registered anatomical imaging to improve localization of uptake.

• Risk of Misdiagnosis in Patients Evaluated for Alzheimer's disease: Consider additional evaluation to confirm the absence of AD pathology in patients with a negative TAUVID scan. (2.6, 5.1)
• Risk of Chronic Traumatic Encephalopathy Misdiagnosis: The safety and effectiveness of TAUVID have not been established for patients being evaluated for CTE. (1, 5.2)
• Radiation Risk: Ensure safe drug handling to protect patients and health care workers from unintentional radiation exposure. (2.1, 5.3)

• Recommended dose is 370 MBq (10 mCi), administered as a bolus intravenous injection. (2.2)
• Initiate imaging approximately 80 minutes after drug administration. (2.3)
• See full prescribing information for additional preparation, administration, imaging, and radiation dosimetry information. (2)

Injection: clear, colorless solution in a 50 mL or 100 mL multiple-dose vial containing 300 MBq/mL to 3,700 MBq/mL (8.1 mCi/mL to 100 mCi/mL) flortaucipir F 18 at the end of synthesis.

TAUVID contains flortaucipir fluorine 18 (F 18). Chemically, flortaucipir F 18 is 7-(6-[F-18]fluoropyridin-3-yl)-5H-pyrido[4,3-b]indole. The molecular weight is 262.27, the molecular formula is C₁₆H₁₀[¹⁸F]N_3, and the structural formula is:

TAUVID is a sterile, non-pyrogenic solution for intravenous injection. The clear, colorless solution free of visible particulate matter is supplied ready to use, and each milliliter contains up to 2 micrograms of flortaucipir and 300 to 3,700 MBq (8.1 to 100 mCi) flortaucipir F 18 at end of synthesis, 1.5 mg of L-cysteine hydrochloride monohydrate USP, 2.1 mg of dibasic sodium phosphate anhydrous USP, up to 55 of micrograms hydrogen chloride and 0.1 mL dehydrated alcohol in 0.9% sodium chloride injection USP. The pH of the solution is between 5.5 and 7.5.

TAUVID is radiolabeled with fluorine 18 (F 18), a cyclotron produced radionuclide that decays by positron emission to stable oxygen 18 with a half-life of 109.8 minutes. The principal photons useful for diagnostic imaging are the coincident pair of 511 keV gamma photons, resulting from the interaction of the emitted positron with an electron (Table 3).

Lactation: Interrupt breastfeeding. Advise a lactating woman to avoid breastfeeding for 4 hours after TAUVID administration. (8.2)

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 [see Clinical Studies (14)]. 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). The adverse reactions reported in ≥ 0.5% of study participants are shown in Table 2.

Adverse reactions with a frequency <0.5% in adults who received TAUVID in clinical trials include:

Nervous system disorders: dysgeusia

Radiation Risk

Advise patients of the radiation risk of TAUVID [see Warnings and Precautions (5.3)].

Pregnancy

Advise a pregnant woman of the potential risks of fetal exposure to radiation doses with TAUVID [see Use in Specific Populations (8.1)].

Lactation

Advise a lactating woman to avoid breastfeeding for 4 hours after TAUVID administration in order to minimize radiation exposure to a breastfed infant [see Use in Specific Populations (8.2)].

Manufactured for Avid Radiopharmaceuticals, a wholly-owned subsidiary of Eli Lilly and Company, Philadelphia, PA 19104

Copyright © 2020, 2024, Eli Lilly and Company. All rights reserved.

TAU-0003-USPI-20240205

TAUVID is a radioactive drug. Only authorized persons qualified by training and experience should receive, use, and administer TAUVID. Handle TAUVID with appropriate safety measures to minimize radiation exposure during administration [see Warnings and Precautions (5.3)]. Use waterproof gloves and effective shielding, including syringe shields, when preparing and handling TAUVID.

• Before interpreting the image, review the brain to determine the lobar anatomy. Interpret the images by first evaluating the temporal lobes, followed by occipital, parietal, and frontal lobes bilaterally.
• To evaluate the temporal lobes, subdivide them into four quadrants by placing the horizontal crosshair immediately posterior to the brainstem nuclei and then scrolling inferiorly to place the vertical crosshair through the widest portion of the temporal pole, thus obtaining the anterolateral temporal (ALT), anterior mesial temporal (AMT), posterolateral temporal (PLT) and posterior mesial temporal (PMT) quadrants. See Figure 2 for an example (the left and right image panels show the same scan in two different color scales).

Figure 2: Temporal Lobe Quadrants

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.

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.

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 [see Clinical Studies (14)].

Limitations of Use

TAUVID is not indicated for use in the evaluation of patients for chronic traumatic encephalopathy (CTE) [see Warnings and Precautions (5.2)].

PACKAGE LABEL – Tauvid 100 mci 50 mL SHIELD

NDC 0002-1220-50

Tauvid™

Flortaucipir F 18 Injection

50 mL Multiple-Dose Vial

Sterile

Rx Only

CAUTION ☢ RADIOACTIVE MATERIAL

300 MBq/mL to 3,700 MBq/mL (8.1 mCi/mL to 100 mCi/mL) at End of Synthesis

For Intravenous Use Only

_____MBq (_____mCi) in _____mL at _____:_____ on _____

Expires at _____:_____ on _____

Batch No._____

Dosage: See prescribing information.

Contains up to 2 micrograms of flortaucipir, 1.5 mg L-cysteine hydrochloride monohydrate USP, 2.1 mg of dibasic sodium phosphate anhydrous USP, up to 55 micrograms of hydrogen chloride and 0.1 mL dehydrated alcohol USP in 0.9% sodium chloride injection USP per milliliter of solution. Store vial upright in a shielding container at 25°C (77°F); excursions permitted to 15°C to 30°C (59°F to 86°F).

Manufactured by PETNET Solutions, Inc. Knoxville, TN 37932 for Avid Radiopharmaceuticals, a wholly-owned subsidiary of Eli Lilly and Company, Philadelphia, PA 19104

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.

The goal of the read is to identify and locate areas of flortaucipir activity in the neocortex that are greater than the background activity (background activity is defined as up to 1.65-fold the measured cerebellar average). For optimal display, select a color scale with a rapid transition between two distinct colors and adjust the scale so that the transition occurs at the 1.65-fold threshold. Examine the posterolateral temporal (PLT), occipital, parietal, and frontal regions bilaterally. Neocortical activity in either hemisphere contributes to image interpretation. Activity in white matter or regions outside the brain does not contribute to image interpretation. To help identify the PLT, consider subdividing the temporal lobe into four quadrants as instructed below. Activity in the anterior and medial temporal lobe does not contribute to image interpretation of a positive TAUVID pattern.

The safety and effectiveness of TAUVID in pediatric patients have not been established.

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.

Diagnostic radiopharmaceuticals, including TAUVID, expose patients to radiation [see Dosage and Administration (2.7)]. 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 [see Dosage and Administration (2.1, 2.2)].

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 [see Dosage and Administration (2.6)].

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 (see Table 5). 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.

Image reader performance for distinguishing B3 (positive) from B0-B2 (negative) tau pathology is shown in Table 6.

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) [see Warnings and Precautions (5.1)].

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.

None.

Most common adverse reactions (frequency ≥ 0.5%) were headache, injection site pain, and increased blood pressure. (6.1)

To report SUSPECTED ADVERSE REACTIONS, contact Eli Lilly and Company at 1-800-LillyRx (1-800-545-5979) or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

The relationship between flortaucipir F 18 plasma concentrations and image interpretation was not explored in clinical trials.

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.

Starting approximately 80 minutes after the TAUVID intravenous injection, obtain a 20-minute PET image 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.

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).

The point source air-kerma coefficient for F18 is 3.74E^-17 Gy m²/(Bq s). The first half-value thickness of lead (Pb) for F 18 gamma rays is approximately 6 mm. The relative reduction of radiation emitted by F 18 that results from various thicknesses of lead shielding is shown in Table 4. The use of 8 cm of Pb will decrease the radiation transmission (i.e., exposure) by a factor of about 10,000.

Radiation absorbed dose estimates are shown in Table 1 for organs and tissues of adults from intravenous administration of TAUVID. The effective radiation dose resulting from administration of 370 MBq (10 mCi) of TAUVID to an adult weighing 70 kg is estimated to be 8.7 mSv. Critical organs include the upper large intestinal wall, small intestine, and liver. When PET/CT is performed, exposure to radiation will increase in an amount dependent on the settings used in the CT acquisition.

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.

Interpret TAUVID imaging independently of the patient's clinical features and other imaging.

Interpret the PET TAUVID images based upon the pattern and density of the radioactive signal within the neocortical gray matter (not within white matter or in regions outside of the brain). Only uptake of tracer in the neocortical grey matter regions should contribute to scan interpretation.

Off-target binding may be seen in the choroid plexus, striatum, and brainstem nuclei. Small foci of noncontiguous tracer uptake may lead to false positive interpretation. Interpret scans that have isolated or noncontiguous, small foci in any region with caution. Some scans may be difficult to interpret due to image noise or motion artifact. For cases where there is uncertainty as to the location of neocortical uptake, use co-registered anatomical imaging to improve localization of uptake.

• Risk of Misdiagnosis in Patients Evaluated for Alzheimer's disease: Consider additional evaluation to confirm the absence of AD pathology in patients with a negative TAUVID scan. (2.6, 5.1)
• Risk of Chronic Traumatic Encephalopathy Misdiagnosis: The safety and effectiveness of TAUVID have not been established for patients being evaluated for CTE. (1, 5.2)
• Radiation Risk: Ensure safe drug handling to protect patients and health care workers from unintentional radiation exposure. (2.1, 5.3)

• Recommended dose is 370 MBq (10 mCi), administered as a bolus intravenous injection. (2.2)
• Initiate imaging approximately 80 minutes after drug administration. (2.3)
• See full prescribing information for additional preparation, administration, imaging, and radiation dosimetry information. (2)

Injection: clear, colorless solution in a 50 mL or 100 mL multiple-dose vial containing 300 MBq/mL to 3,700 MBq/mL (8.1 mCi/mL to 100 mCi/mL) flortaucipir F 18 at the end of synthesis.

TAUVID contains flortaucipir fluorine 18 (F 18). Chemically, flortaucipir F 18 is 7-(6-[F-18]fluoropyridin-3-yl)-5H-pyrido[4,3-b]indole. The molecular weight is 262.27, the molecular formula is C₁₆H₁₀[¹⁸F]N_3, and the structural formula is:

TAUVID is a sterile, non-pyrogenic solution for intravenous injection. The clear, colorless solution free of visible particulate matter is supplied ready to use, and each milliliter contains up to 2 micrograms of flortaucipir and 300 to 3,700 MBq (8.1 to 100 mCi) flortaucipir F 18 at end of synthesis, 1.5 mg of L-cysteine hydrochloride monohydrate USP, 2.1 mg of dibasic sodium phosphate anhydrous USP, up to 55 of micrograms hydrogen chloride and 0.1 mL dehydrated alcohol in 0.9% sodium chloride injection USP. The pH of the solution is between 5.5 and 7.5.

TAUVID is radiolabeled with fluorine 18 (F 18), a cyclotron produced radionuclide that decays by positron emission to stable oxygen 18 with a half-life of 109.8 minutes. The principal photons useful for diagnostic imaging are the coincident pair of 511 keV gamma photons, resulting from the interaction of the emitted positron with an electron (Table 3).

Lactation: Interrupt breastfeeding. Advise a lactating woman to avoid breastfeeding for 4 hours after TAUVID administration. (8.2)

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 [see Clinical Studies (14)]. 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). The adverse reactions reported in ≥ 0.5% of study participants are shown in Table 2.

Adverse reactions with a frequency <0.5% in adults who received TAUVID in clinical trials include:

Nervous system disorders: dysgeusia

Radiation Risk

Advise patients of the radiation risk of TAUVID [see Warnings and Precautions (5.3)].

Pregnancy

Advise a pregnant woman of the potential risks of fetal exposure to radiation doses with TAUVID [see Use in Specific Populations (8.1)].

Lactation

Advise a lactating woman to avoid breastfeeding for 4 hours after TAUVID administration in order to minimize radiation exposure to a breastfed infant [see Use in Specific Populations (8.2)].

Manufactured for Avid Radiopharmaceuticals, a wholly-owned subsidiary of Eli Lilly and Company, Philadelphia, PA 19104

Copyright © 2020, 2024, Eli Lilly and Company. All rights reserved.

TAU-0003-USPI-20240205

TAUVID is a radioactive drug. Only authorized persons qualified by training and experience should receive, use, and administer TAUVID. Handle TAUVID with appropriate safety measures to minimize radiation exposure during administration [see Warnings and Precautions (5.3)]. Use waterproof gloves and effective shielding, including syringe shields, when preparing and handling TAUVID.

• Before interpreting the image, review the brain to determine the lobar anatomy. Interpret the images by first evaluating the temporal lobes, followed by occipital, parietal, and frontal lobes bilaterally.
• To evaluate the temporal lobes, subdivide them into four quadrants by placing the horizontal crosshair immediately posterior to the brainstem nuclei and then scrolling inferiorly to place the vertical crosshair through the widest portion of the temporal pole, thus obtaining the anterolateral temporal (ALT), anterior mesial temporal (AMT), posterolateral temporal (PLT) and posterior mesial temporal (PMT) quadrants. See Figure 2 for an example (the left and right image panels show the same scan in two different color scales).

Figure 2: Temporal Lobe Quadrants

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.

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.

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 [see Clinical Studies (14)].