Florbetaben F 18

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)

Injection: 50 MBq/mL to 5,000 MBq/mL (1.4 mCi/mL to 135 mCi/mL) of florbetaben F 18 in up to 50 mL volume at end of synthesis (EOS) as a clear solution in a multiple-dose vial. Injection: 50 MBq/mL to 5,000 MBq/mL (1.4 mCi/mL to 135 mCi/mL) of florbetaben F 18 in up to 50 mL volume at end of synthesis in a multiple-dose vial

None None.

Risk of Image Misinterpretation and Other Errors: Image interpretation errors have been observed. (5.1) Radiation Risk: NEURACEQ contributes to a patient’s long-term cumulative radiation exposure. Ensure safe drug handling to protect patients and health care providers from unintentional radiation exposure. Advise patients to hydrate before and after administration and to void frequently after administration. (2.1, 2.2, 5.2)

5.1 Risk of Image Misinterpretation and Other Errors Errors may occur in the estimation of brain amyloid beta neuritic plaque density during NEURACEQ image interpretation [ see Clinical Studies ( 14 ) ]. The use of clinical information in the interpretation of NEURACEQ images has not been evaluated and may lead to an inaccurate assessment. Severe brain atrophy as well as motion artifacts that result in image distortion may limit the ability to distinguish gray and white matter on a NEURACEQ scan. Perform image interpretation independently of the patient’s clinical information. For cases where there is uncertainty as to the location of cortical signal, use co-registered anatomical imaging to improve localization of signal [see Dosage and Administration ( 2.4 )] .

5.2 Radiation Risk NEURACEQ 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 drug handling to protect patients and health care providers from unintentional radiation exposure. Advise patients to hydrate before and after administration and to void frequently after administration [ see Dosage and Administration ( 2.1 , 2.2 )] .

5.1 Risk of Image Misinterpretation and Other Errors Errors may occur in the estimation of brain amyloid beta neuritic plaque density during NEURACEQ image interpretation [ see Clinical Studies ( 14 ) ]. The use of clinical information in the interpretation of NEURACEQ images has not been evaluated and may lead to an inaccurate assessment. Severe brain atrophy as well as motion artifacts that result in image distortion may limit the ability to distinguish gray and white matter on a NEURACEQ scan. Perform image interpretation independently of the patient’s clinical information. For cases where there is uncertainty as to the location of cortical signal, use co-registered anatomical imaging to improve localization of signal [see Dosage and Administration ( 2.4 )] .

5.2 Radiation Risk NEURACEQ 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 drug handling to protect patients and health care providers from unintentional radiation exposure. Advise patients to hydrate before and after administration and to void frequently after administration [ see Dosage and Administration ( 2.1 , 2.2 )] .

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 Lantheus Biosciences Ltd., a Lantheus company, 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

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

8.1 Pregnancy Risk Summary There are no available data on NEURACEQ 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 florbetaben F 18 to evaluate its effect on female reproduction and embryo-fetal development. All radiopharmaceuticals, including NEURACEQ, have the potential to cause fetal harm depending on the stage of fetal development and the magnitude of the radiation dose. If considering NEURACEQ 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 birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.

8.2 Lactation Risk Summary There are no data on the presence of florbetaben F 18 in human milk, the effects on the breastfed infant, or the effects on milk production. Exposure of NEURACEQ 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 NEURACEQ and any potential adverse effects on the breastfed child from NEURACEQ 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 after administration of NEURACEQ Lactation: Temporarily discontinue breastfeeding. A lactating woman should pump and discard breast milk for 24 hours after NEURACEQ administration (8.2).

8.4 Pediatric Use The safety and effectiveness of NEURACEQ have not been established in pediatric patients.

8.5 Geriatric Use Of the 872 subjects in clinical studies of NEURACEQ, 603 (69%) subjects were 65 years of age and older, while 304 (35%) subjects were 75 years of age and older. No overall differences in safety or effectiveness were observed between subjects 65 years of age and older and younger adult subjects.

8.1 Pregnancy Risk Summary There are no available data on NEURACEQ 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 florbetaben F 18 to evaluate its effect on female reproduction and embryo-fetal development. All radiopharmaceuticals, including NEURACEQ, have the potential to cause fetal harm depending on the stage of fetal development and the magnitude of the radiation dose. If considering NEURACEQ 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 birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.

8.2 Lactation Risk Summary There are no data on the presence of florbetaben F 18 in human milk, the effects on the breastfed infant, or the effects on milk production. Exposure of NEURACEQ 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 NEURACEQ and any potential adverse effects on the breastfed child from NEURACEQ 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 after administration of NEURACEQ Lactation: Temporarily discontinue breastfeeding. A lactating woman should pump and discard breast milk for 24 hours after NEURACEQ administration (8.2).

8.4 Pediatric Use The safety and effectiveness of NEURACEQ have not been established in pediatric patients.

8.5 Geriatric Use Of the 872 subjects in clinical studies of NEURACEQ, 603 (69%) subjects were 65 years of age and older, while 304 (35%) subjects were 75 years of age and older. No overall differences in safety or effectiveness were observed between subjects 65 years of age and older and younger adult subjects.