Amyvid (Page 3 of 5)

7 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 Amyvid image results.

Within a clinical study of patients with a range of cognitive impairment, some patients with probable AD were receiving the following medications: donepezil, galantamine, memantine. Mean cortical Standardized Uptake Value (SUV) ratios did not differ between the patients taking or not taking these concomitant medications. In in vitro tests, none of the drugs tested, including the acetylcholinesterase inhibitors donepezil, galantamine, and tacrine, altered florbetapir F 18 binding to its target.

8 USE IN SPECIFIC POPULATIONS

8.1 Pregnancy

Risk Summary

There are no available data on Amyvid use in pregnant women to evaluate for a drug-associated risk of major birth defects, miscarriage or adverse maternal or fetal outcomes. Animal reproduction studies have not been conducted with Amyvid to evaluate its effect on female reproduction and embryo-fetal development. All radiopharmaceuticals, including Amyvid, have a potential to cause fetal harm depending on the stage of fetal development and the magnitude of the radiopharmaceutical dose. If considering Amyvid administration to a pregnant woman, inform the patient about the potential for adverse pregnancy outcomes based on the radiation dose from the drug and the gestational timing of exposure.

The background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of adverse outcomes. The background risk in the U.S. general population of major birth defects is 2-4% and of miscarriage is 15-20% of clinically recognized pregnancies.

8.2 Lactation

Risk Summary

There are no data on the presence of Florbetapir F 18 Injection in human milk, the effects on the breastfed infant, or the effects of Florbetapir F 18 Injection on milk production. Lactation studies have not been conducted in animals. Exposure of Amyvid to a breastfed infant can be minimized by temporary discontinuation of breastfeeding [see Clinical Considerations]. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for Amyvid and any potential adverse effects on the breastfed child from Amyvid or from the underlying maternal condition.

Clinical Considerations

To decrease radiation exposure to the breastfed infant, advise a lactating woman to pump and discard breast milk for 24 hours (>10 half-lives of radioactive decay for the F 18 isotope) following administration of Amyvid.

8.3 Females and Males of Reproductive Potential

Assess pregnancy status before administering Amyvid to a female of reproductive potential.

8.4 Pediatric Use

Amyvid is not indicated for use in pediatric patients.

8.5 Geriatric Use

Of 496 patients in completed clinical studies of Amyvid, 307 patients were ≥65 years old (203 patients were over 75 years of age). No overall differences in safety or effectiveness were observed between these subjects and younger subjects.

11 DESCRIPTION

Amyvid contains florbetapir F 18, a molecular imaging agent that binds to β-amyloid aggregates, and is intended for use with PET imaging of the brain. Chemically, florbetapir F 18 is described as (E)-4-(2-(6-(2-(2-(2[18 F] fluoroethoxy)ethoxy)ethoxy)pyridine-3-yl)vinyl)-N-methylbenzamine. The molecular weight is 359 and the structural formula is:

Structural Formula
(click image for full-size original)

Amyvid is a sterile, non-pyrogenic radioactive diagnostic agent for intravenous injection. The clear, colorless solution is supplied ready to use and each milliliter contains 0.1 to 19 micrograms of florbetapir and 500 — 1900 MBq (13.5 — 51 mCi) florbetapir F 18 at EOS, 4.5 mg sodium ascorbate USP and 0.1 mL dehydrated alcohol USP in 0.9% sodium chloride injection USP. The pH of the solution is between 5.5 and 8.0.

11.1 Physical Characteristics

Amyvid is radiolabeled with [18 F] fluorine (F 18) that decays by positron (β+) emission to O 18 and has a half-life of 109.77 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).

Table 3: Principal Radiation Produced from Decay of Fluorine 18
Radiation Energy Level (keV) Abundance (%)
Positron 249.8 96.9
Gamma 511 193.5

11.2 External Radiation

The point source air-kerma coefficienta for F-18 is 3.74E -17 Gy m2 /(Bq s); this coefficient was formerly defined as the specific gamma-ray constant of 5.7 R/hr/mCi at 1 cm. The first half-value thickness of lead (Pb) for F 18 gamma rays is approximately 6 mmb. 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.

Table 4: Radiation Attenuation of 511 keV Gamma Rays by Lead Shielding

a Eckerman KF and A Endo. MIRD: Radionuclide Data and Decay Schemes, 2nd Edition, 2008.

b Derived from data in NCRP Report No. 49. 1998, Appendix C

Shield Thickness cm of lead (Pb) Coefficient of Attenuation
0.6 0.5
2 0.1
4 0.01
6 0.001
8 0.0001

12 CLINICAL PHARMACOLOGY

12.1 Mechanism of Action

Florbetapir F 18 binds to β-amyloid plaques and the F 18 isotope produces a positron signal that is detected by a PET scanner. In in vitro binding studies using postmortem human brain homogenates containing β-amyloid plaques, the dissociation constant (Kd ) for florbetapir was 3.7 ± 0.3 nM. The binding of florbetapir F 18 to β-amyloid aggregates was demonstrated in postmortem human brain sections using autoradiographic methods, thioflavin S and traditional silver staining correlation studies as well as monoclonal antibody β-amyloid-specific correlation studies. Florbetapir binding to tau protein and a battery of neuroreceptors was not detected in in vitro studies.

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