DRUG INTERACTIONS(details)

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

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U.S. FDA APPROVED DRUGS SURING 2020                                        

Serial No   20

Name of the Drug-    CERIANNA

Active Ingredient -   Fluvoestridol

Pharmacological Classification- Diagnostic  imaging of  Certain patients  with                                                                  Brain cancer                                                                                                                                                                                                                

Date of Approval-          May 2020                                                    

HIGHLIGHTS OF PRESCRIBING INFORMATION-

These highlights do not include all the information needed to use CERIANNA™ safely and effectively. See full prescribing information for CERIANNA. CERIANNA™ (fluoroestradiol F 18) Injection, for intravenous use

Initial U.S. Approval: 2020

INDICATIONS AND USAGE-

­ 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). 

DOSAGE 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) ---------------------

DOSAGE FORMS AND STRENGTHS---------------------­ Injection: 148 MBq/mL to 3,700 MBq/mL (4 mCi/mL to 100 mCi/mL) of fluoroestradiol F 18 in a multiple-dose vial. (3)

---------------------------CONTRAINDICATIONS------------------------------­ • None. (4) ------------------------WARNINGS 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) -------------------------------ADVERSE REACTIONS-----------------------------­ Reported adverse reactions include: injection-site pain and dysgeusia To report SUSPECTED ADVERSE REACTIONS, contact Zionexa US Corp at +1.844.946.6392 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. (6) ------------------------------DRUG INTERACTIONS-------------------------------­ • Drugs such as tamoxifen and fulvestrant that block the estrogen receptor reduce the uptake of fluoroestradiol F 18. Do not delay indicated therapy in order to administer CERIANNA. Image patients with CERIANNA prior to starting systemic endocrine therapies that block ER. (2.3, 7.1) --------------------------USE IN SPECIFIC POPULATIONS--------------------­ • Lactation: Interrupt breastfeeding. Advise a lactating woman to avoid breastfeeding for 4 hours after CERIANNA administration. (8.2) See 17 for PATIENT COUNSELING INFORMATION. Revised:05/202

DOSAGE 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) ---------------------

DOSAGE FORMS AND STRENGTHS---------------------­ Injection: 148 MBq/mL to 3,700 MBq/mL (4 mCi/mL to 100 mCi/mL) of fluoroestradiol F 18 in a multiple-dose vial. (3)

CLINICAL PHARMACOLOGY 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 Distribution After intravenous injection, 95% of fluoroestradiol F 18 is bound to plasma proteins. Fluoroestradiol F 18 distributes primarily to hepatobiliary system, and also to small and large intestines, heart wall, blood, kidney, uterus and bladder. Metabolism Fluoroestradiol F 18 is metabolized in the liver. At 20 minutes after injection, approximately 20% of circulating radioactivity in the plasma is in the form of non-metabolized fluoroestradiol F 18. At 2 hours after injection, circulating fluoroestradiol F 18 levels are less than 5% of peak concentration. Reference ID: 4610145 Excretion Elimination is by biliary and urinary excretion.

13 NONCLINICAL TOXICOLOGY 13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility Carcinogenesis No long-term studies in animals were performed to evaluate the carcinogenic potential of CERIANNA. Mutagenesi

 USE IN SPECIFIC POPULATIONS

1. Pregnancy Risk Summary-

All radiopharmaceuticals, including CERIANNA, have the potential to cause fetal harm depending on the fetal stage of development and the magnitude of radiation dose.

Advise a pregnant woman of the potential risks of fetal exposure to radiation from administration of CERIANNA.

 All pregnancies have a background risk of birth defects, 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 2-4% and 15-20%, respectively. 

2. Lactation Risk Summary-                                                                                        There are no data on the presence of fluoroestradiol F 18 in human milk, or its effects on the breastfed infant or milk production.

Lactation studies have not been conducted in animals. Advise a lactating woman to avoid breastfeeding for 4 hours after CERIANNA administration in order to minimize radiation exposure to a breastfed infant.

3. Pediatric Use-                                                                                                           The safety and effectiveness of CERIANNA in pediatric patients have not been established.

4. 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 DESCRIPTION 11.1 Chemical Characteristics CERIANNA contains fluoroestradiol fluorine 18 (F 18), a synthetic estrogen analog. Chemically, fluoroestradiol F 18 is [18F]16a-fluoro-3,17ß-diol-estratriene-1,3,5(10). The molecular weight is 289.37, and the structural formula is: