Neuraceq

Florbetaben F 18 injection is used in adults to help diagnose Alzheimer's disease and other cognitive (mental) problems. It is used in for procedure called positron emission tomography (PET) scan to help your doctor see an image of your brain.

Florbetaben F 18 is a radiopharmaceutical. Radiopharmaceuticals are radioactive agents, which may be used to find and treat certain diseases or to study the function of the body's organs.

This medicine is to be given only by or under the direct supervision of a doctor with specialized training in nuclear medicine.

It is very important that your doctor check your progress very closely while you are receiving this medicine. This will allow your doctor to see if the medicine is working properly and to decide if you should continue to receive it.

While receiving this medicine, you will be exposed to radiation. If you have any questions about this, talk to your doctor.

It is important to tell your doctor that you are pregnant or breastfeeding before using this medicine.

Along with its needed effects, a medicine may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor or nurse immediately if any of the following side effects occur:

• Fast heartbeat
• fever
• hives, itching, or rash
• hoarseness
• irritation
• joint pain, stiffness, or swelling
• redness of the skin
• swelling of the eyelids, face, lips, hands, or feet
• tightness in the chest
• troubled breathing or swallowing

Some side effects may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

• Pain, redness, or skin irritation at the injection site

Other side effects not listed may also occur in some patients. If you notice any other effects, check with your healthcare professional.

Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

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 rate observed in clinical practice.

The overall safety profile of Neuraceq is based on data from 1090 administrations of Neuraceq to 872 subjects. No serious adverse reactions related to Neuraceq administration have been reported. The most frequently observed adverse drug reactions in subjects receiving Neuraceq were injection site reactions consisting of erythema, irritation and pain. All adverse reactions were mild to moderate in severity and of short duration. The most commonly reported adverse reactions (occurring in at least 1% of subjects) during Neuraceq clinical trials are shown in Table 2.

Pregnancy

Pregnancy Category C: It is not known whether Neuraceq can cause fetal harm when administered to a pregnant woman or if it can affect reproduction capacity. Animal reproduction studies have not been conducted with Neuraceq. All radiopharmaceuticals, including Neuraceq, have a potential to cause fetal harm. The likelihood of fetal harm depends on the stage of fetal development and the magnitude of the radiopharmaceutical dose. Neuraceq should be given to a pregnant woman only if clearly needed. Assess pregnancy status before administering Neuraceq to a female of reproductive potential.

Nursing Mothers

It is not known whether Neuraceq is excreted in human milk. Because many drugs are excreted into human milk and because of the potential for radiation exposure to nursing infants from Neuraceq, avoid use of the drug in a breastfeeding mother or have the mother temporarily interrupt breastfeeding for 24 hours (>10 half-lives of radioactive decay for the F 18 isotope) after exposure to Neuraceq. If breastfeeding is interrupted, the patient should pump and discard her breast milk and use alternate nutrition sources (e.g. stored breast milk or infant formula) for 24 hours after the administration of Neuraceq.

Pediatric Use

Neuraceq is not indicated for use in pediatric patients.

Geriatric Use

Of the 872 subjects in clinical studies of Neuraceq, 603 (69%) were 65 years or over, while 304 (35%) were 75 years or over. No overall differences in safety were observed between these subjects and younger subjects.

A pharmacological overdose of Neuraceq is unlikely given the relatively low doses used for diagnostic purposes.

In the event of administration of a radiation overdose with Neuraceq, the absorbed organ dose to the patient should be reduced by increasing elimination of the radionuclide from the body by inducing frequent micturition.

Neuraceq contains florbetaben F18, a molecular imaging agent that binds to β-amyloid plaques in the brain, and is intended for use with PET imaging. Chemically, florbetaben F18 is described as 4-[(E)-2-(4-{2-[2-(2-[18F] fluoroethoxy) ethoxy] ethoxy}phenyl)vinyl]-N-methylaniline. The molecular weight is 358.45 and the structural formula is:

Neuraceq is a sterile, non-pyrogenic radioactive diagnostic agent for intravenous injection. The clear solution is supplied ready to use. Each mL contains up to 3 micrograms and 50-5000 MBq (1.4 – 135 mCi) florbetaben F18 EOS, 4.4 mg ascorbic acid, 118 mg ethanol, 200 mg macrogol 400, 28.8 mg sodium ascorbate. The pH of the solution is between 4.5 and 7.

Physical Characteristics

Neuraceq is radiolabeled with [18F] fluorine (F18) that decays by positron (ß+) emission to O 18 and has 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).

External Radiation

The point source air-kerma coefficienta for F18 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 for F18-fluorine gamma rays is approximately 6 mmb. The relative reduction of radiation emitted by F18-fluorine that results from various thicknesses of lead shielding is shown in Table 4. The use of ~8 cm of lead (Pb) will decrease the radiation transmission (i.e. exposure) by a factor of about 10,000.

aEckerman KF and A Endo. MIRD: Radionuclide Data and Decay Schemes, 2nd Edition, 2008.
bDerived from data in NCRP Report No. 49. 1998, Appendix C

NDC 54828-001-30

Neuraceq™

Florbetaben F18 injection

30 mL Multiple-Dose Vial

Sterile Non-Pyrogenic

Rx ONLY

CAUTION

RADIOACTIVE MATERIAL

Activity at *EOS _______MBq (_______mCi) in _______mL at ___:___on _________

Expiration Date/Time _____ _________                                                 Volume: 29mL

(Expires 10 Hours after *EOS) Concentration at *EOS____________mCi/mL

Diagnostic - For Intravenous Use Only

Batch No.:____________________________________ Date:__________________

Each mL contains up to 3 mcg of florbetaben and 50 - 5000 MBq/mL (1.4 - 135 mCi/mL) florbetaben F18 at *EOS, 4.4 mg ascorbic acid, 118 mg ethanol, 200 mg macrogol (PEG400), 28.8 mg sodium ascorbate, 677.5 mg water for injection. *EOS - End of Synthesis

Store at room temperature 25°C (77°F); excursions permitted to 2°C to 42°C (36°F – 108°F).

Store upright. Do not use if it is cloudy or contains particulate matter.

Manufactured by Zevacor Pharma, Inc., 21000 Atlantic Blvd., Ste. 730, Dulles, VA 20166 for Piramal Imaging SA

SPF-061-V03

NDC 54828-001-30

Neuraceq™

Florbetaben F18 injection

30 mL Multiple-Dose Vial

Sterile Non-Pyrogenic

Rx ONLY

CAUTION

RADIOACTIVE MATERIAL

Activity at *EOS _______MBq (_______mCi) in _______mL at ___:___on _________

Batch No.:____________________________________ Date:__________________

Expiration Date/Time _____ _________                                                 Volume: 29mL

(Expires 10 Hours after *EOS) Concentration at *EOS____________mCi/mL

Diagnostic - For Intravenous Use Only

Each mL contains up to 3 mcg of florbetaben and 50 - 5000 MBq/mL (1.4 - 135 mCi/mL) florbetaben F18 at *EOS, 4.4 mg ascorbic acid, 118 mg ethanol, 200 mg macrogol (PEG400), 28.8 mg sodium ascorbate, 677.5 mg water for injection. See package insert for dosage information. Dispense aseptically into a sterile syringe or other sterile container within a lead shielded secondary container.

Store room temperature 25°C (77°F); excursions permitted to 2°C to 42°C (36°F – 108°F). Store upright. Do not use if it is cloudy or contains particulate matter. *EOS - End of Synthesis

Manufactured by Zevacor Pharma, Inc., 21000 Atlantic Blvd., Ste. 730, Dulles, VA 20166 for Piramal Imaging SA

SPF-060-V03

Applies to florbetaben f-18: intravenous solution

Along with its needed effects, florbetaben f-18 (the active ingredient contained in Neuraceq) may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor or nurse immediately if any of the following side effects occur while taking florbetaben f-18:

• Fast heartbeat
• fever
• hives, itching, or rash
• hoarseness
• irritation
• joint pain, stiffness, or swelling
• redness of the skin
• swelling of the eyelids, face, lips, hands, or feet
• tightness in the chest
• troubled breathing or swallowing

Some side effects of florbetaben f-18 may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

• Pain, redness, or skin irritation at the injection site