Florbetaben

1 INDICATIONS AND USAGE NEURACEQ is indicated for positron emission tomography (PET) of the brain to estimate amyloid beta neuritic plaque density in adults with cognitive impairment for: Evaluation of Alzheimer’s disease (AD) and other causes of cognitive decline Selection of patients who are indicated for amyloid beta-directed therapy as described in the prescribing information of the therapeutic products NEURACEQ is a radioactive diagnostic drug indicated for positron emission tomography (PET) of the brain to estimate amyloid beta neuritic plaque density in adults with cognitive impairment for: Evaluation of Alzheimer’s disease (AD) and other causes of cognitive decline Selection of patients who are indicated for amyloid beta-directed therapy as described in the prescribing information of the therapeutic products (1)

2 DOSAGE AND ADMINISTRATION The recommended amount of radioactivity is 300 MBq (8.1 mCi) administered as a slow single intravenous bolus (6 sec/mL) in a total volume of up to 10 mL. (2.2) Follow the injection with an intravenous flush of approximately 10 mL of 0.9% sodium chloride injection. (2.2) Obtain 15-minute to 20-minute PET images starting approximately 45 minutes to 130 minutes after drug administration. (2.3) See full prescribing information for image interpretation and radiation dosimetry. (2.4, 2.5) 2.1 Radiation Safety - Drug Handling Handle NEURACEQ with appropriate safety measures to minimize radiation exposure during administration [ see Warnings and Precautions ( 5.2 )]. Use waterproof gloves and effective radiation shielding, including lead-glass syringe shields when handling and administering NEURACEQ. Radiopharmaceuticals, including NEURACEQ, should be used by or under the control of healthcare providers 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. 2.2 Recommended Dosing and Administration Instructions Recommended Dosage The recommended amount of radioactivity of NEURACEQ is 300 MBq (8.1 mCi) in a total volume of up to 10 mL, administered as a single slow intravenous bolus (6 sec/mL). The maximum mass dose is 30 micrograms. Follow the administration with an intravenous flush of approximately 10 mL of 0.9% sodium chloride injection. Patient Preparation Instruct patients to hydrate before and after NEURACEQ administration and to void before imaging and frequently thereafter following NEURACEQ administration [see Warnings and Precautions ( 5.2 ) ] . Administration Use aseptic technique and radiation shielding to withdraw and administer NEURACEQ. Visually inspect NEURACEQ for particulate matter and discoloration prior to administration. Do not use NEURACEQ if it contains particulate matter or if it is discolored. Do not dilute NEURACEQ. Measure the activity of NEURACEQ with a dose calibrator immediately prior to injection. Verify patency of the indwelling catheter by a test flush with 0.9% sodium chloride injection prior to administration of NEURACEQ. Dispose of unused product in a safe manner in compliance with applicable regulations 2.3 Image Acquisition Guideline Position the patient supine with the head positioned to center the brain, including the cerebellum, in the PET scanner field of view. Tape or other flexible head restraints may be employed to reduce head movement. Acquire 15-minute to 20-minute PET images starting 45 minutes to 130 minutes after NEURACEQ administration. Image reconstruction should include attenuation correction with resulting transaxial pixel sizes between 2 mm and 3 mm. 2.4 Image Display and Interpretation Image Display Display images in the transaxial orientation using gray scale or inverse gray scale. The sagittal and coronal planes may be used for additional orientation purposes. CT or MR images may be helpful for anatomic reference purposes. However, visual assessment should be performed using the axial planes according to the recommended reading methodology. Locate regions which ‘anatomically’ correspond to white matter structures (e.g., the cerebellar white matter or the splenium) for orientation. Review images in a systematic manner, starting with the cerebellum and scrolling up through the lateral temporal and frontal lobes, the posterior cingulate cortex/precuneus, and the parietal lobes. Visual Assessment NEURACEQ images should be interpreted only by readers who successfully complete training provided by the manufacturer. The reader training can be accessed here: https://www.neuraceqreadertraining.com/learn. Perform image interpretation independently of the patient’s clinical features, relying on the recognition of unique image features. Interpret NEURACEQ images based upon the distribution of signal intensity within the cerebral cortex by comparing the signal intensity in the cortical gray matter and the adjacent white matter. Signal intensity in the gray matter is assessed in the following four brain regions: the temporal lobes, the frontal lobes, the posterior cingulate cortex/precuneus, and the parietal lobes. For a gray matter cortical region to be assessed as showing increased signal, the majority of slices from the respective region must be affected. The signal intensity in the cerebellum does not contribute to the scan interpretation. For example, a positive scan may show retained cerebellar gray-white contrast even when the cortical gray-white contrast is lost. Some scans may be difficult to interpret due to image noise, atrophy with a thinned cortex, or image blur. If co-registered computerized tomography (CT) or magnetic resonance (MR) images are available, the CT/MR images may be used to clarify the relationship of the NEURACEQ uptake and the gray m

6 ADVERSE REACTIONS Most common adverse reactions (incidence ≥ 1%) were injection site pain, injection site erythema, and injection site irritation (6.1). To report SUSPECTED ADVERSE REACTIONS, contact Life Molecular Imaging at 1‑833-491-2524 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 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 clinical practice. The safety of NEURACEQ was evaluated in 872 adult subjects who received NEURACEQ by intravenous injection in clinical trials. Of these subjects, 724 received a single dose, 78 received two doses, and 70 received three doses at yearly intervals as part of annual repeat scanning. Table 2 shows adverse reactions reported in 1% of these 1,090 administrations from the clinical trials. Table 2: Adverse Reactions Reported in 1% of NEURACEQ Administrations in Adults in Clinical Trials Adverse Reaction NEURACEQ N=1,090 Administrations % Injection site pain 3.4 Injection site erythema 1.7 Injection site irritation 1.1