FLUOROESTRADIOL F-18: 11 Adverse Event Reports & Safety Profile

11 DESCRIPTION

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 5.5 to 8.0. 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.

Chemical

Structure

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).

Table

2.

Principal Radiation Produced From

Decay of Fluorine 18 Radiation Radiation Energy Level (keV) % Abundance Positron 249.8

96.9 Gamma 511 193.5

11.3 External Radiation The point source air-kerma coefficient for F 18 is 3.75 × 10 -17 Gy m 2 / (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.

Table

3.

Radiation

Attenuation of 511 keV Gamma Rays by Lead Shielding 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

AND USAGE CERIANNA is indicated for use with positron emission tomography (PET) imaging for the detection of estrogen receptor (ER)-positive lesions as an adjunct to biopsy in patients with recurrent or metastatic breast cancer. CERIANNA is a radioactive diagnostic agent indicated for use with positron emission tomography (PET) imaging for the detection of estrogen receptor (ER)-positive lesions as an adjunct to biopsy in patients with recurrent or metastatic breast cancer. ( 1 ) 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). ( 1 , 5.1 ) 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).

AND ADMINISTRATION Recommended dose is 222 MBq (6 mCi), with a range of 111 MBq to 222 MBq (3 mCi to 6 mCi), administered as an intravenous injection over 1 to 2 minutes. ( 2.2 ) Recommended imaging start time is 80 minutes (range 20 minutes to 80 minutes) after drug administration. ( 2.4 ) See full prescribing information for additional preparation, administration, imaging, and radiation dosimetry information. ( 2 )

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 <span class="opacity-50 text-xs">[see Warnings and Precautions (5.2) ]</span> . Use waterproof gloves and effective radiation shielding, including syringe shields, when preparing and handling CERIANNA.

2.2 Recommended Dosage and Administration Instructions Recommended Dosage The recommended amount of radioactivity to be administered for PET imaging is 222 MBq (6 mCi), with a range of 111 MBq to 222 MBq (3 mCi to 6 mCi), administered as a single intravenous injection of 10 mL or less over 1 to 2 minutes. Preparation and Administration For patient preparation instructions, see Dosage and Administration 2.3 . Use aseptic technique and radiation shielding when withdrawing and administering CERIANNA. Visually inspect the radiopharmaceutical solution. Do not use if it contains particulate matter or if it is cloudy or discolored (CERIANNA is a clear, colorless solution). CERIANNA may be diluted with 0.9% Sodium Chloride Injection, USP. Assay the dose in a suitable dose calibrator prior to administration. Post-Administration Instructions Follow the CERIANNA injection with an intravenous flush of 0.9% Sodium Chloride injection, USP. Dispose of any unused CERIANNA in compliance with applicable regulations.

2.3 Patient Preparation Assessment for Drug Interactions Before administering CERIANNA, discontinue drugs that bind to ER (e.g., selective estrogen receptor modulators (SERMs) and selective estrogen receptor down-regulators (SERDs)) <span class="opacity-50 text-xs">[see Drug Interactions (7) ]</span> .

Patient

Hydration and Voiding 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.

Pregnancy Status

Assessment of pregnancy status is recommended in females of reproductive potential before administering CERIANNA.

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.

Table

1.

Estimated Radiation Absorbed

Doses in Various Organs/Tissues in Adults Who Received FLUOROESTRADIOL F 18 Organ Mean Absorbed Dose Per Unit of Activity Administered (mGy/MBq) Adrenals

0.023 Brain

0.01 Breasts

0.009 Gallbladder

0.102 Lower large intestine

0.012 Small intestine

0.027 Stomach

0.014 Upper large intestine

0.03 Heart wall

0.026 Kidney

0.035 Liver

0.126 Lungs

0.017 Muscle

0.021 Ovaries

0.018 Pancreas

0.023 Red Marrow

0.013 Bone surface

0.014 Skin

0.005 Spleen

0.015 Testes

0.012 Thymus

0.014 Thyroid

0.012 Urinary bladder

0.05 Uterus

0.039 Lens

0.009 Effective dose = 0.022 mSv/MBq

None . None. ( 4 )

REACTIONS Reported adverse reactions include: injection-site pain and dysgeusia ( 6 ) To report SUSPECTED ADVERSE REACTIONS, contact GE HealthCare at 1-800-654-0118 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 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 &lt; 1%: General disorders : injection-site pain Neurological and gastrointestinal disorders : dysgeusia

AND PRECAUTIONS Risk of Misdiagnosis . Do not use CERIANNA in lieu of biopsy when biopsy is indicated in patients with recurrent or metastatic breast cancer. Pathology or clinical characteristics that suggest a patient may benefit from systemic hormone therapy should take precedence over a discordant negative CERIANNA scan. ( 5.1 )

Radiation

Risks . Ensure safe drug handling and patient preparation procedures to protect patients and health care providers from unintentional radiation exposure. ( 2.1 , 2.3 , 5.2 )

5.1 Risk of Misdiagnosis Inadequate Tumor Characterization and Other ER-Positive Pathology Breast cancer may be heterogeneous within patients and across time. CERIANNA images ER and is not useful for imaging other receptors such as HER2 and PR. The uptake of fluoroestradiol F 18 is not specific for breast cancer and may occur in a variety of ER-positive tumors that arise outside of the breast, including from the uterus and ovaries. Do not use CERIANNA in lieu of biopsy when biopsy is indicated in patients with recurrent or metastatic breast cancer.

False

Negative CERIANNA Scan A negative CERIANNA scan does not rule out ER-positive breast cancer [see Clinical Studies (14) ] . Pathology or clinical characteristics that suggest a patient may benefit from systemic hormone therapy should take precedence over a discordant negative CERIANNA scan.

5.2 Radiation Risks Diagnostic radiopharmaceuticals, including CERIANNA, expose patients to radiation <span class="opacity-50 text-xs">[see Dosage and Administration (2.6) ]</span> . 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 <span class="opacity-50 text-xs">[see Dosage and Administration (2.1) and (2.3) ]</span> .

INTERACTIONS Drugs that bind to the estrogen receptor (ER) may compete with the binding of fluoroestradiol F 18 and may reduce the detection of ER-positive lesions with CERIANNA. Before administering CERIANNA, discontinue drugs that bind to the ER, such as SERMs and SERDs, for at least 5 biological half-lives (e.g., elacestrant for 11 days, tamoxifen for 8 weeks, and fulvestrant for 28 weeks) [see Dosage and Administration (2.3) ] . Before administering CERIANNA, discontinue drugs that bind to the ER, such as SERMs and SERDs, for at least 5 biological half-lives (e.g., elacestrant for 11 days, tamoxifen for 8 weeks, and fulvestrant for 28 weeks). ( 2.3 , 7 )