Amyvid - Florbetapir F 18 injection, Solution

AMYVID 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

• The recommended amount of radioactivity is 370 MBq (10 mCi) administered as a single intravenous bolus in a total volume of up to 10 mL. (
  2.2 Recommended Dosage and Administration Instructions

  Recommended Dosage

  The recommended amount of radioactivity of AMYVID is 370 MBq (10 mCi) in a total volume of up to 10 mL, administered as a single intravenous bolus. The maximum mass dose is 50 mcg. Follow the injection with an intravenous flush of approximately 10 mL of 0.9% sodium chloride injection.

  Patient Preparation

  Instruct patients to hydrate before and after AMYVID administration and to void following AMYVID administration before imaging and frequently thereafter

  [see Warnings and Precautions ]

  .

  Administration

  • Use aseptic technique and radiation shielding when withdrawing and administering AMYVID.
  • Visually inspect AMYVID for particulate matter and discoloration prior to administration. Do not use AMYVID if it contains particulate matter or if it is discolored.
  • Do not dilute AMYVID.
  • Assay the dose in a dose calibrator prior to administration.
  • Inject AMYVID through a short intravenous catheter (approximately 1.5 inches or less) to minimize the potential for adsorption of the drug to the catheter. Portions of the AMYVID dose may adhere to longer catheters.
  • Dispose of unused product in a safe manner in compliance with applicable regulations.
  )
• Follow the injection with an intravenous flush of approximately 10 mL of 0.9% sodium chloride injection. (
  2.2 Recommended Dosage and Administration Instructions

  Recommended Dosage

  The recommended amount of radioactivity of AMYVID is 370 MBq (10 mCi) in a total volume of up to 10 mL, administered as a single intravenous bolus. The maximum mass dose is 50 mcg. Follow the injection with an intravenous flush of approximately 10 mL of 0.9% sodium chloride injection.

  Patient Preparation

  Instruct patients to hydrate before and after AMYVID administration and to void following AMYVID administration before imaging and frequently thereafter

  [see Warnings and Precautions ]

  .

  Administration

  • Use aseptic technique and radiation shielding when withdrawing and administering AMYVID.
  • Visually inspect AMYVID for particulate matter and discoloration prior to administration. Do not use AMYVID if it contains particulate matter or if it is discolored.
  • Do not dilute AMYVID.
  • Assay the dose in a dose calibrator prior to administration.
  • Inject AMYVID through a short intravenous catheter (approximately 1.5 inches or less) to minimize the potential for adsorption of the drug to the catheter. Portions of the AMYVID dose may adhere to longer catheters.
  • Dispose of unused product in a safe manner in compliance with applicable regulations.
  )
• Obtain 10-minute PET images starting approximately 30 minutes to 50 minutes after drug administration. (
  2.3 Image Acquisition Instructions

  • 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 10-minute PET images starting 30 minutes to 50 minutes after AMYVID administration.
  • Image reconstruction should include attenuation correction with resulting transaxial pixel sizes between 2 mm and 3 mm.
  )
• See full prescribing information for image interpretation and radiation dosimetry. (
  2.4 Image Display and Interpretation

  Image Display

  • Display images in the transaxial orientation with access as needed to the sagittal and coronal planes.
  • In reviewing the images, include all transaxial slices of the brain using a black-white scale set to the maximum intensity of all the brain pixels.
  • Initially locate the brain slice with the highest levels of image contrast (highest signal intensity) and adjust the contrast appropriately.
  • Start image interpretation by displaying slices sequentially from the bottom of the brain to the top. Periodically refer to the sagittal and coronal plane image display as needed to better define the signal intensity and to ensure that the entire brain is displayed.

  Visual Assessment

  AMYVID images should be interpreted only by readers who successfully complete the training program provided by the manufacturer.

  Perform image interpretation independently of the patient's clinical features, relying on the recognition of unique image features.

  Interpret AMYVID 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. 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 cortical ribbon, or image blur. For cases where there is uncertainty as to the location of cortical signal, use co-registered anatomical imaging to improve localization of signal

  [see Warnings and Precautions ]

  .

  Negative AMYVID Scan

  Negative scans show more signal in white matter than in adjacent cortical gray matter, creating clear gray-white contrast.

  A negative scan indicates sparse to no amyloid beta neuritic plaques. In patients being evaluated for AD and other causes of cognitive decline who have not been treated with amyloid beta-directed therapy, a negative scan is inconsistent with a neuropathological diagnosis of AD at the time of image acquisition and reduces the likelihood that a patient's cognitive impairment is due to AD. A negative scan result does not preclude the accumulation of amyloid beta in the brain in the future.

  Positive AMYVID Scan

  Positive scans show cortical areas with reduction or loss of the normally distinct gray-white contrast. These scans will have one or more areas with increased cortical gray matter signal which results in reduced (or absent) gray-white contrast. Specifically, a positive scan will have either:

  • a)Two or more brain areas (each larger than a single cortical gyrus) in which there is reduced or absent gray-white contrast. This is the most common appearance of a positive scan.
    
    
    or
  • b)One or more areas in which cortical gray matter signal is intense and clearly exceeds the signal in adjacent white matter.

  A positive scan establishes the presence of moderate to frequent amyloid beta neuritic plaques. Neuropathological examination has shown that moderate to frequent amyloid beta neuritic plaques are present in patients with AD, but may also be present in patients with other types of neurologic conditions as well as older people with normal cognition.

  Figures 1, 2, and 3 provide examples of negative and positive scans.

  

  Figure 1: Examples of AMYVID negative scans (top two rows) and positive scans (bottom two rows).

  Left to right panels show sagittal, coronal, and transverse PET image slices. Final panel to right shows an enlarged picture of the brain area under the box. The top two arrows are pointing to normal preserved gray-white contrast with cortical signal intensity less than the adjacent white matter. The bottom two arrows indicate areas of decreased gray-white contrast with increased cortical signal intensity that is comparable to the intensity in the adjacent white matter.

  Figure 2: Typical Negative Scan. The upper (top) and lower (bottom) transverse slices both show good gray-white matter contrast. The dotted lines illustrate the edge of the cortical gray matter (outer line) and the gray-white border (inner line) and highlight the contrast between less intense signal in the gray matter and more intense signal in the white matter. The arrows illustrate the following points: A. White matter tracts can be delineated from the frontal lobe to parietal lobe. B. White matter tracts are clearly identified throughout the occipital / temporal area. C. Scalloped appearance is seen with “fingers” of white matter in the frontal cortex. D. Low levels of signal in scalp or skull are distinguished from gray matter signal by the shape and position.

  Figure 3: Typical Positive Scan: The upper (top) and lower (bottom) transverse slices show loss of gray-white matter contrast in multiple brain regions. The dotted lines illustrate the edge of the cortical gray matter. Compared to the images from the negative case in Figure 2, the gray matter signal is similar to white matter signal and the gray-white matter border is more difficult to discern. The arrows show the following points: A. White matter tracts are difficult to fully identify as they travel from frontal to parietal lobe. B. Borders of white matter tracts in occipital / temporal area are lost in places. C. Gray matter in medial parietal cortex (precuneus) has increased signal. D. Low levels of signal in scalp or skull are distinguished from gray matter signal by the shape and position.

  

  

  

  Quantitative Analysis

  Quantification of amyloid beta neuritic plaque levels (e.g., Centiloid scale or standardized uptake value ratio (SUVR)) can be used in conjunction with visual assessment and performed with FDA-authorized software indicated for quantification of brain amyloid beta PET scans. Refer to the drug manufacturer's training materials for qualitative and quantitative assessment and software manufacturers' documentation for software operation.
  ,
  2.5 Radiation Dosimetry

  Estimated radiation absorbed doses for adults from intravenous injection of AMYVID are shown in Table 1.

  Table 1: Estimated Radiation Absorbed Doses in Organs/Tissues in Adults Who Received AMYVID

  ORGAN/TISSUE	MEAN ABSORBED DOSE PER UNIT ADMINISTERED ACTIVITY (microGy/MBq)
  Adrenal	14
  Brain	10
  Breasts	6
  Gallbladder Wall	143
  Heart Wall	13
  Kidneys	14
  Liver	64
  Lower Large Intestine Wall	28
  Lungs	9
  Muscle	9
  Osteogenic Cells	28
  Ovaries	18
  Pancreas	14
  Red Marrow	14
  Skin	6
  Small Intestine	66
  Spleen	9
  Stomach Wall	12
  Testes	7
  Thymus	7
  Thyroid	7
  Upper Large Intestine Wall	74
  Urinary Bladder Wall	27
  Uterus	16
  Total Body	12
  Effective Dose (microSv/MBq)	19

  The whole-body effective dose resulting from administration of 370 MBq (10 mCi) of AMYVID to an adult is estimated to be 7 mSv. When PET/CT is performed, exposure to radiation will increase by an amount dependent on the settings used in the CT acquisition.
  )

Injection: 500 MBq/mL to 1,900 MBq/mL (13.5 mCi/mL to 51 mCi/mL) of florbetapir F 18 in up to 100 mL volume at end of synthesis (EOS) as a clear, colorless solution in a multiple-dose vial.

Lactation: Temporarily discontinue breastfeeding. A lactating woman should pump and discard breast milk for 24 hours after AMYVID administration. (