Cerianna Injection Prescribing Information

Limitations of Use

Tissue biopsy should be used to confirm recurrence of breast cancer and to verify ER status by pathology. CERIANNA is not useful for imaging other receptors, such as human epidermal growth factor receptor 2 (HER2) and the progesterone receptor (PR).

2.1 Radiation Safety - Drug Handling

CERIANNA is a radioactive drug. Only authorized persons qualified by training and experience should receive, use, and administer CERIANNA. Handle CERIANNA with appropriate safety measures to minimize radiation exposure during administration [see Warnings and Precautions (5.2)]. Use waterproof gloves and effective radiation shielding, including syringe shields, when preparing and handling CERIANNA.

2.2 Recommended Dosage and Administration Instructions

2.3 Patient Preparation

2.4 Image Acquisition

Position the patient supine with arms above the head, if possible. The recommended start time for image acquisition is 80 minutes after the intravenous administration of CERIANNA. Scan duration adapted from the range of 20 minutes to 30 minutes and imaging start times adapted within the range of 20 minutes to 80 minutes may be customized according to the equipment used and patient and tumor characteristics for optimal image quality.

2.5 Image Interpretation

Uptake of fluoroestradiol F 18 depends on ER density and function in tumors and physiologic tissue, including in liver, ovary, and uterus. Detection of ER-positive tumors should be based on comparison with tissue background outside of organs with high physiologic uptake and regions with high activity due to hepatobiliary and urinary excretion.

2.6 Radiation Dosimetry

Radiation absorbed dose estimates are shown in Table 1 for organs and tissues of adults from intravenous administration of CERIANNA. The radiation effective dose resulting from administration of 222 MBq (6 mCi) of CERIANNA to an adult weighing 70 kg is estimated to be 4.9 mSv. Critical organs include the liver, gallbladder, and uterus. When PET/CT is performed, exposure to radiation will increase by an amount dependent on the settings used for the CT acquisition.

5.1 Risk of Misdiagnosis

5.2 Radiation Risks

Diagnostic radiopharmaceuticals, including CERIANNA, expose patients to radiation [see Dosage and Administration (2.6)]. Radiation exposure is associated with a dose-dependent increased risk of cancer. Ensure safe drug handling and patient preparation procedures to protect patients and health care providers from unintentional radiation exposure [see Dosage and Administration (2.1) and (2.3)].

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 practice.

The safety of CERIANNA was evaluated from published clinical studies of 1,207 patients with breast cancer receiving at least one fluoroestradiol F 18 administration. The following adverse reactions occurred at a rate < 1%:

• General disorders: injection-site pain
• Neurological and gastrointestinal disorders: dysgeusia

7.1 Systemic Endocrine Therapies that Target Estrogen Receptors

Certain classes of systemic endocrine therapies, including ER modulators and ER down-regulators, block ER, reduce the uptake of fluoroestradiol F 18, and may reduce detection of ER-positive lesions after administration of CERIANNA. Drugs from these classes such as tamoxifen and fulvestrant may block ER for up to 8 and 28 weeks, respectively. Do not delay indicated therapy in order to administer CERIANNA. Administer CERIANNA prior to starting systemic endocrine therapies that block ER [see Dosage and Administration (2.3)].

8.1 Pregnancy

8.2 Lactation

8.4 Pediatric Use

The safety and effectiveness of CERIANNA in pediatric patients have not been established.

8.5 Geriatric Use

Clinical studies of fluoroestradiol F 18 injection did not reveal any difference in pharmacokinetics or biodistribution in patients aged 65 and over.

11.1 Chemical Characteristics

CERIANNA contains fluoroestradiol fluorine 18 (F 18), a synthetic estrogen analog. Chemically, fluoroestradiol F 18 is [18F]16α-fluoro-3,17β-diol-estratriene-1,3,5(10). The molecular weight is 289.37, and the structural formula is:

CERIANNA is a sterile, clear, colorless solution for intravenous injection, with an osmolarity of 340 mOsm. Its pH ranges between 4.5 to 7.0. The composition of the final product in 40 mL solution is fluoroestradiol no more than 5 mcg, fluoroestradiol F 18 148 MBq/mL to 3,700 MBq/mL (4 mCi/mL to 100 mCi/mL), sodium ascorbate 0.44% w/v in sodium chloride 0.9% w/v, and ethanol no more than 3.2% w/v.

11.2 Physical Characteristics

CERIANNA is radiolabeled with F 18, a cyclotron produced radionuclide that decays by positron emission to stable oxygen 18 with 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 2).

11.3 External Radiation

The point source air-kerma coefficient for F 18 is 3.75 × 10-17 Gy m2 / (Bq s). The first half-value thickness of lead (Pb) for F 18 gamma rays is approximately 6 mm. The relative reduction of radiation emitted by F 18 that results from various thicknesses of lead shielding is shown in Table 3. The use of 8 cm Pb decreases the radiation transmission (i.e., exposure) by a factor of about 10,000.

12.1 Mechanism of Action

Fluoroestradiol F 18 binds ER. The following binding affinity: Kd = 0.13 ± 0.02 nM, Bmax = 1901 ± 89 fmol/mg, and IC50 = 0.085 nM, was determined in an ER-positive human breast cancer cell line (MCF-7).

12.2 Pharmacodynamics

The relationship between fluoroestradiol F18 plasma concentrations and image interpretation has not been studied. Fluoroestradiol F18 uptake measured by PET in human tumors is directly proportional to tumor ER expression measured by in vitro assays.

12.3 Pharmacokinetics

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility

16.1 How Supplied

CERIANNA is supplied in a 50 mL multiple-dose glass vial (NDC 72874-001-01) containing a clear, colorless injection solution at a strength of 148 MBq/mL to 3,700 MBq/mL (4 mCi/mL to 100 mCi/mL) fluoroestradiol F 18 at the end of synthesis. Each vial contains multiple doses and is enclosed in a shield container to minimize external radiation exposure.

16.2 Storage and Handling

Radiation Risks

Advise patients of the radiation risks of CERIANNA [see Warnings and Precautions (5.2)]. Instruct patients to drink water to ensure adequate hydration prior to administration of CERIANNA and to continue drinking and voiding frequently during the first hours following administration to reduce radiation exposure [see Dosage and Administration (2.3)].

Pregnancy

Advise a pregnant woman of the potential risks of fetal exposure to radiation doses with CERIANNA [see Use in Specific Populations (8.1)].

Lactation

Advise a lactating woman to avoid breastfeeding for 4 hours after CERIANNA administration in order to minimize radiation exposure to a breastfed infant [see Use in Specific Populations (8.2)].