Flutemetamol F 18

Flutemetamol F 18
Adult Indications & Dosage
Pediatric Indications & Dosage
Contraindications
Warnings & Precautions
Adverse Reactions
Drug Interactions
Use in Specific Populations
Administration & Monitoring
Overdosage
Pharmacology
Clinical Studies
How Supplied
Images
Patient Counseling Information
Precautions with Alcohol
Brand Names
Look-Alike Names

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Rabin Bista, M.B.B.S. [2]

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Overview

Flutemetamol F 18 is a Diagnostic Agent that is FDA approved for the diagnosis of Positron Emission Tomography (PET) imaging of the brain to estimate β amyloid neuritic plaque density in adult patients with cognitive impairment who are being evaluated for Alzheimer's disease (AD). Common adverse reactions include flushing, headache, hypertension, nausea, and dizziness.

Adult Indications and Dosage

FDA-Labeled Indications and Dosage (Adult)

Indications

Vizamyl is indicated for Positron Emission Tomography (PET) imaging of the brain to estimate β amyloid neuritic plaque density in adult patients with cognitive impairment who are being evaluated for Alzheimer's Disease (AD) and other causes of cognitive decline.

A negative Vizamyl scan indicates sparse to no neuritic plaques and is inconsistent with a neuropathological diagnosis of AD at the time of image acquisition; a negative scan result reduces the likelihood that a patient's cognitive impairment is due to AD. A positive Vizamyl scan indicates moderate to frequent amyloid neuritic plaques; neuropathological examination has shown this amount of amyloid neuritic plaque is present in patients with AD, but may also be present in patients with other types of neurologic conditions as well as in older people with normal cognition. Vizamyl is an adjunct to other diagnostic evaluations.

Limitations of Use:

A positive Vizamyl scan does not establish a diagnosis of AD or other cognitive disorder. Safety and effectiveness of Vizamyl have not been established for: Predicting development of dementia or other neurologic condition. Monitoring responses to therapies.

Dosage

Radiation Safety - Drug Handling Vizamyl is a radioactive drug and should be handled with safety measures to minimize radiation exposure during administration [see WARNINGS AND PRECAUTIONS (5.3)]. Use waterproof gloves and effective shielding, including lead-glass syringe shields when handling and administering Vizamyl. To minimize radiation dose to the bladder, encourage patients to hydrate before and after Vizamyl administration in order to permit frequent voiding. Encourage patients to void before and after imaging with Vizamyl and frequently thereafter for 24 hours following Vizamyl administration.

Radiopharmaceuticals, including Vizamyl, should be used by or under the control of physicians who are qualified by specific training and experienced 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.

2.2 Recommended Dosing and Administration Procedures The recommended dose for Vizamyl is 185 megabecquerels (MBq) [5 millicuries (mCi)] in a maximum dose volume of 10 mL, administered as a single intravenous bolus within 40 seconds. The maximum mass dose is 20 micrograms. Follow the injection with an intravenous flush of 5 to 15 mL of 0.9% sterile sodium chloride injection.

Use aseptic technique and radiation shielding to withdraw and administer Vizamyl solution. Calculate the necessary volume to administer based on calibration time and dose using a suitably calibrated instrument. Visually inspect Vizamyl for particulate matter and discoloration prior to administration. Do not administer Vizamyl if it contains particulate matter or is discolored [see DESCRIPTION (11)]. Do not dilute Vizamyl. Dispose of unused product in a safe manner in compliance with applicable regulations [see HOW SUPPLIED/STORAGE AND HANDLING (16)]. 2.3 Imaging Acquisition Guidelines A 20-minute PET image should be acquired starting 90 minutes after Vizamyl injection, using a PET scanner in 3-D mode with appropriate data corrections. Position the patient supine with the brain (including the cerebellum) within a single field of view. The patient's head should be tilted so that the anterior commissure-posterior commissure (AC-PC) plane is at right angles to the bore-axis of the PET scanner, with the head positioned in a suitable head support. Reducing head movement with tape or other flexible head restraints may be employed.

Iterative or filtered back-projection reconstruction is recommended with a slice thickness of 2 to 4 mm, matrix size of 128 x 128 with pixel sizes of approximately 2 mm. Where a post-smoothing filter is applied, a full width half maximum (FWHM) of not more than 5 mm is recommended; filter FWHM should be chosen to optimize the signal-to-noise ratio while preserving the sharpness of the reconstructed image.

2.4 Image Orientation and Display Image Orientation

Orient axial and coronal images to show symmetry of brain structures, with equal heights of structures bilaterally. Orient sagittal images so that the head and neck are neither flexed nor extended; the anterior and posterior aspects of the corpus callosum should be parallel to the AC-PC line as shown in Figure 2.

Image Display

Display images with all planes (axial, sagittal and coronal planes) linked by crosshairs. Select a color scale that provides a progression of low through high intensity (e.g., rainbow or Sokoloff). The selected color scale should (1) provide colors that allow the reader to discriminate intensity levels above and below the intensity level of the pons, (2) provide a color for regions with little or no amyloid binding such as the cerebellar cortex, and (3) provide a range of at least five distinct colors above 50 to 60% of the peak intensity. Display the reference scale. Adjust the color scale to set the pons to approximately 90% maximum intensity. The cerebellar cortex should represent approximately 20-30% of peak intensity on both negative and positive Vizamyl scans. Briefly display axial brain slices from bottom to top and look for signs of atrophy. Systematically review the following brain regions (recommended plane) for flutemetamol F18 uptake as described in Image Interpretation below: Frontal lobes (axial, with optional sagittal plane view) Posterior cingulate and precuneus (sagittal, with optional coronal plane view) Lateral temporal lobes (axial, with optional coronal plane view) Inferolateral parietal lobes (coronal, with optional axial plane view) Striatum (axial, with optional sagittal plane view) 2.5 Image Interpretation Vizamyl images should be interpreted only by readers who successfully complete the electronic training program provided by the manufacturer [see WARNINGS AND PRECAUTIONS (5.2)]. The objective of Vizamyl image interpretation is to provide an estimate of the brain β-amyloid neuritic plaque density, not to make a clinical diagnosis. Image interpretation is performed independently of a patient's clinical features and relies upon recognition of image features in certain brain regions.

Image interpretation is based upon the distribution of radioactive signal within the brain; clinical information is not a component of image assessment [see WARNINGS AND PRECAUTIONS (5.2)]. Images are designated as positive or negative either by comparing radioactivity in cortical grey matter with activity in adjacent white matter, or based on the intensity in the five regions mentioned above. Signal uptake in the cerebellum does not contribute to scan interpretation (for example, a positive scan may show retained cerebellar grey-white contrast even when the cortical grey-white contrast is lost). Images should be viewed with the minimum image intensity set to zero and the maximum set such that the signal level in the easily identifiable pons is at 90% of maximum.

Negative scans show more radioactivity in white matter than in grey matter, creating clear grey-white matter contrast.

Specifically, a negative scan would have the following characteristics:

frontal, lateral temporal, inferolateral parietal lobes: gradual gradient from bright intensity of the white matter to lower intensity at the periphery of the brain; distinct sulci with concave surfaces (white matter sulcal pattern),

and

posterior cingulate and precuneus: grey matter uptake below 50-60% of peak intensity; gap of lower intensity separates two hemispheres on coronal view,

and

striatum: approximately 50% of peak intensity or lower in the region between the higher intensities of the thalamus and frontal white matter (striatal "gap") Positive scans show at least one cortical region with reduction or loss of the normally distinct grey-white matter contrast. These scans have one or more regions with increased cortical grey matter signal (above 50-60% peak intensity) and/or reduced (or absent) grey-white matter contrast (white matter sulcal pattern is less distinct). A positive scan may have one or more regions in which grey matter radioactivity is as intense or exceeds the intensity in adjacent white matter.

Specifically, a positive scan would have the following characteristics:

frontal, lateral temporal, or inferolateral parietal lobes: high intensity seen to the periphery of the brain, with sharp reduction of intensity at the brain margin; sulci not distinct due to fill-in by high intensity grey matter resulting in a convex surface at the edge of the brain,

or

posterior cingulate and precuneus: grey matter uptake above 50-60% of peak intensity; high grey matter intensity that closes the gap between the two hemispheres on coronal view,

or

striatum: intensity above 50-60% of peak intensity; gap between thalamus and frontal white matter not distinct

If any one of the brain regions systematically reviewed for flutemetamol F18 uptake (see IMAGE ORIENTATION AND DISPLAY above) is positive in either hemisphere, then the scan is considered positive. Otherwise, the scan is considered negative. Among patients with clinically important β-amyloid neuritic plaques in the brain, the temporal lobes, parietal lobes, and striatum may not be as affected compared to other brain regions. Therefore, in some images, flutemetamol F18 signal in these regions may not be as intense as in the frontal lobes or the posterior cingulate and precuneus regions.

Atrophy may affect the interpretability of scans, particularly in the frontal, temporal and parietal lobes [see WARNINGS AND PRECAUTIONS (5.2)]. For cases in which atrophy is apparent or suspected and there is uncertainty as to the location of the grey matter on the PET scan, examine the striatum for flutemetamol F18 signal as it is less affected by atrophy than other regions of the brain.

If the patient's MRI or CT brain images are available the interpreter should examine the CT or MRI images to clarify the relationship between PET flutemetamol F18 uptake and grey matter anatomy.

Other factors that may affect the ability to interpret Vizamyl images include patient factors such as brain pathology, surgical changes, post-radiation therapy changes, and implants. Some scans may be difficult to interpret due to image noise, suboptimal patient positioning, or over-smoothing of the reconstructed image.

Figure 1: Axial view of negative (left) and positive (right) Vizamyl scans. The axial slices which cut through the frontal pole and inferior aspect of the splenium are shown using a rainbow color scale. The left image shows a white matter sulcal pattern at the frontal (f) and lateral temporal (lt) regions with a color intensity that tapers to the periphery, as well as less radioactivity in the striatal region(s). The right image shows absence of the white matter sulcal pattern with intensity radiating to a sharply defined convex edge, as well as more radioactivity in the striatum. In both the frontal and lateral temporal regions, the intensity is higher in the grey matter regions of the right image compared to those of the left image.

Off-Label Use and Dosage (Adult)

Guideline-Supported Use

There is limited information regarding Off-Label Guideline-Supported Use of Flutemetamol F 18 in adult patients.

Non–Guideline-Supported Use

There is limited information regarding Off-Label Non–Guideline-Supported Use of Flutemetamol F 18 in adult patients.

Pediatric Indications and Dosage

FDA-Labeled Indications and Dosage (Pediatric)

Safety and efficacy has not been established in pediatrics patient.

Off-Label Use and Dosage (Pediatric)

Guideline-Supported Use

There is limited information regarding Off-Label Guideline-Supported Use of Flutemetamol F 18 in pediatric patients.

Non–Guideline-Supported Use

There is limited information regarding Off-Label Non–Guideline-Supported Use of Flutemetamol F 18 in pediatric patients.

Contraindications

• Vizamyl is contraindicated in patients with a history of hypersensitivity reaction to Vizamyl, polysorbate 80, or any other inactive ingredient in Vizamyl

Warnings

Hypersensitivity Reactions Hypersensitivity reactions such as flushing and dyspnea have been observed within minutes following Vizamyl administration. These reactions may occur in patients with no history of prior exposure to Vizamyl.

Before administering Vizamyl, ask patients about prior reactions to drugs, especially those containing polysorbate 80.

Have resuscitation equipment and trained personnel immediately available at the time of Vizamyl administration [see CONTRAINDICATIONS (4)].

5.2 Risk for Image Misinterpretation and Other Errors Errors may occur while using Vizamyl PET images to estimate brain neuritic plaque density [see CLINICAL STUDIES (14)].

Image interpretation is performed independently of the patient's clinical information. The use of clinical information in the interpretation of Vizamyl images has not been evaluated and may lead to errors. Extensive brain atrophy may limit the ability to distinguish grey and white matter on a Vizamyl scan [see DOSAGE AND ADMINISTRATION (2.5)]. Motion artifacts may distort the image [see DOSAGE AND ADMINISTRATION (2.3)].

Vizamyl scan results are indicative of the brain neuritic amyloid plaque content only at the time of image acquisition and a negative scan result does not preclude the development of brain amyloid in the future.

5.3 Radiation Risk Vizamyl, similar to other radiopharmaceuticals, contributes to a patient's overall long-term cumulative radiation exposure. Long-term cumulative radiation exposure is associated with an increased risk of cancer. Ensure safe handling to protect patients and health care workers from unintentional radiation exposure

Adverse Reactions

Clinical Trials Experience

Clinical Trials Experience Clinical trials are conducted under widely varying conditions and adverse reaction rates observed in the clinical trials of Vizamyl cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice.

In clinical trials, 761 adults (367 men and 394 women, 91% Caucasian) with a mean age of 62 years (range 18-93 years) received Vizamyl. Most subjects (530, 70%) received a dose of 185 MBq (5 mCi).

One subject out of 761 administered Vizamyl experienced a serious hypersensitivity reaction with flushing, dyspnea and chest pressure within minutes following Vizamyl administration and recovered with treatment.

Most adverse reactions were mild to moderate in intensity and resolved spontaneously. The most commonly reported adverse reactions (occurring in at least 1% of subjects) in Vizamyl-treated subjects are shown in Table 2.

Postmarketing Experience

There is limited information regarding Postmarketing Experience of Flutemetamol F 18 in the drug label.

Body as a Whole

Cardiovascular

Digestive

Endocrine

Hematologic and Lymphatic

Metabolic and Nutritional

Musculoskeletal

Neurologic

Respiratory

Skin and Hypersensitivy Reactions

Special Senses

Urogenital

Miscellaneous

Drug Interactions

• Pharmacodynamic drug-drug interaction studies have not been performed in patients to establish the extent, if any, to which concomitant medications may alter Vizamyl image results.

Within a clinical study of patients with a range of cognitive impairment, some patients were receiving the following medications: donepezil, galantamine, memantine, rivastigmine. Mean cortical Standardized Uptake Value (SUV) ratios did not differ between the patients taking or not taking these concomitant medications.

Use in Specific Populations

Pregnancy

Pregnancy Category (FDA):

• Pregnancy Category

Pregnancy Category (AUS):

• Australian Drug Evaluation Committee (ADEC) Pregnancy Category

There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Flutemetamol F 18 in women who are pregnant.

Labor and Delivery

There is no FDA guidance on use of Flutemetamol F 18 during labor and delivery.

Nursing Mothers

There is no FDA guidance on the use of Flutemetamol F 18 with respect to nursing mothers.

Pediatric Use

There is no FDA guidance on the use of Flutemetamol F 18 with respect to pediatric patients.

Geriatic Use

There is no FDA guidance on the use of Flutemetamol F 18 with respect to geriatric patients.

Gender

There is no FDA guidance on the use of Flutemetamol F 18 with respect to specific gender populations.

Race

There is no FDA guidance on the use of Flutemetamol F 18 with respect to specific racial populations.

Renal Impairment

There is no FDA guidance on the use of Flutemetamol F 18 in patients with renal impairment.

Hepatic Impairment

There is no FDA guidance on the use of Flutemetamol F 18 in patients with hepatic impairment.

Females of Reproductive Potential and Males

There is no FDA guidance on the use of Flutemetamol F 18 in women of reproductive potentials and males.

Immunocompromised Patients

There is no FDA guidance one the use of Flutemetamol F 18 in patients who are immunocompromised.

Administration and Monitoring

Administration

• Oral

• Intravenous

Monitoring

There is limited information regarding Monitoring of Flutemetamol F 18 in the drug label.

• Description

IV Compatibility

There is limited information regarding IV Compatibility of Flutemetamol F 18 in the drug label.

Overdosage

Acute Overdose

Signs and Symptoms

• Description

Management

• Description

Chronic Overdose

There is limited information regarding Chronic Overdose of Flutemetamol F 18 in the drug label.

Pharmacology

There is limited information regarding Flutemetamol F 18 Pharmacology in the drug label.

Mechanism of Action

Structure

File:Flutemetamol F 1801.png

This image is provided by the National Library of Medicine.

Pharmacodynamics

There is limited information regarding Pharmacodynamics of Flutemetamol F 18 in the drug label.

Pharmacokinetics

There is limited information regarding Pharmacokinetics of Flutemetamol F 18 in the drug label.

Nonclinical Toxicology

There is limited information regarding Nonclinical Toxicology of Flutemetamol F 18 in the drug label.

Clinical Studies

There is limited information regarding Clinical Studies of Flutemetamol F 18 in the drug label.

How Supplied

Storage

There is limited information regarding Flutemetamol F 18 Storage in the drug label.

Images

Drug Images

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Package and Label Display Panel

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Patient Counseling Information

There is limited information regarding Patient Counseling Information of Flutemetamol F 18 in the drug label.

Precautions with Alcohol

• Alcohol-Flutemetamol F 18 interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.

Brand Names

• ®

Look-Alike Drug Names

• A® — B®

Drug Shortage Status

Price

References

The contents of this FDA label are provided by the National Library of Medicine.

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