POSLUMA

1 INDICATIONS AND USAGE POSLUMA is indicated for positron emission tomography (PET) of prostate-specific membrane antigen (PSMA) positive lesions in men with prostate cancer with suspected metastasis who are candidates for initial definitive therapy. with suspected recurrence based on elevated serum prostate-specific antigen (PSA) level. POSLUMA is a radioactive diagnostic agent indicated for positron emission tomography (PET) of prostate-specific membrane antigen (PSMA) positive lesions in men with prostate cancer: with suspected metastasis who are candidates for initial definitive therapy with suspected recurrence based on elevated serum prostate-specific antigen (PSA) level. ( 1 )

2 DOSAGE AND ADMINISTRATION Recommended amount of radioactivity of POSLUMA is 296 MBq (8 mCi) administered as an intravenous bolus injection. ( 2.2 ) Initiate imaging approximately 60 minutes after administration. Scanning should start from mid-thigh and proceed to base of skull. ( 2.4 ) See full prescribing information for additional preparation, handling, administration, imaging, and radiation dosimetry information. ( 2.3 , 2.4 ) 2.1 Radiation Safety - Drug Handling Handle POSLUMA with safety measures to minimize radiation exposure [ see Warnings and Precautions ( 5.2 )] . Use waterproof gloves, effective radiation shielding, including syringe shields, and other appropriate safety measures when handling and administering POSLUMA. Radiopharmaceuticals should be used by or under the control of physicians who are qualified by specific training and experience in the safe use and handling of radionuclides, and whose experience and training have been approved by the appropriate governmental agency authorized to license the use of radionuclides. 2.2 Recommended Dose and Administration Instructions Recommended Dose The recommended amount of radioactivity to be administered in adults is 296 MBq (8 mCi) as an intravenous bolus injection. Preparation and Administration Instructions Inspect POSLUMA visually for particulate matter and discoloration before administration. Do not use the drug if the solution contains particulate matter or is discolored. Use aseptic technique and radiation shielding when withdrawing and administering POSLUMA. Calculate the necessary volume to administer based on calibration time and required dose. The recommended maximum volume of undiluted POSLUMA is 5 mL. POSLUMA may be diluted with 0.9% Sodium Chloride Injection, USP. Assay the dose in a dose calibrator before administration. Post Administration Instructions After the POSLUMA injection, administer an intravenous flush of sterile 0.9% Sodium Chloride Injection, USP to ensure full delivery of the dose. Dispose of any unused drug in a safe manner in compliance with applicable regulations. 2.3 Patient Preparation Instruct patients to drink water prior to administration of POSLUMA to ensure adequate hydration and to continue drinking and voiding frequently for the first few hours following administration to reduce radiation exposure. 2.4 Image Acquisition Patients should void immediately prior to imaging. Position the patient supine with arms above the head. Begin image acquisition approximately 60 minutes after POSLUMA injection. Image acquisition should start from mid-thigh and proceed to the base of the skull. Scan duration is approximately 20 minutes depending on the number of bed positions and acquisition time per bed position (typically 3 minutes). Adapt imaging technique according to the equipment used and patient characteristics in order to obtain the best image quality possible. 2.5 Image Display and Interpretation POSLUMA binds to PSMA. PET images obtained using POSLUMA indicate the presence of PSMA in tissues [see Clinical Pharmacology ( 12.1 )] . Lesions should be considered suspicious if uptake is greater than physiologic uptake in that tissue or greater than adjacent background if no physiologic uptake is expected. Tumors that do not express PSMA will not be visualized. Increased uptake in tumors is not specific for prostate cancer [see Warnings and Precautions ( 5.1 )]. 2.6 Radiation Dosimetry Estimated absorbed radiation doses for adult patients following intravenous injection of POSLUMA are shown in Table 1 . The effective radiation dose resulting from the administration of the recommended activity of 296 MBq of POSLUMA is 4.1 mSv. The radiation absorbed doses to the critical organs of adrenal glands, kidneys, and submandibular glands for the recommended activity of 296 MBq are 54.3 mGy, 51 mGy, and 43.8 mGy, respectively. When PET/CT is performed, exposure to radiation will increase by an amount dependent on the settings used in the CT acquisition. Table 1: Estimated Radiation Absorbed Doses in Organs/Tissues in Adults who Received POSLUMA * The absorbed dose value reflects self-irradiation only; no dose contribution from other regions to the glands is added. ** A 1-hour bladder voiding interval is assumed. Organ/Tissue Absorbed Dose per Unit Administered Activity (mGy/MBq) Mean Adrenal glands 0.184 Brain 0.002 Breasts 0.004 Gallbladder wall 0.017 Lower large intestine wall 0.007 Upper large intestine wall 0.01 Heart wall 0.02 Kidneys 0.172 Lacrimal glands 0.08 * Liver 0.062 Lungs 0.01 Muscle 0.006 Osteogenic cells 0.012 Ovaries 0.005 Pancreas 0.028 Parotid glands 0.114 * Red bone marrow 0.01 Skin 0.002 Small intestine 0.012 Spleen 0.083 Stomach wall 0.012 Sublingual glands 0.065 * Submandibular glands 0.148 * Testes 0.005 Thymus gland 0.01 Thyroid 0.01 Urinary bladder wall 0.006 ** Uterus 0.011 Effective dose (mSv/MBq) 0.014 **

4 CONTRAINDICATIONS None. None. ( 4 )

5 WARNINGS AND PRECAUTIONS Risk of Image Misinterpretation: Image interpretation errors can occur with POSLUMA imaging. Interpretation of POSLUMA PET may differ depending on imaging readers in patients with suspected recurrence of prostate cancer. Consider multidisciplinary consultation and histopathological confirmation. ( 5.1 , 14.2 ) Radiation risk: POSLUMA contributes to a patient's long-term cumulative radiation exposure. Ensure safe handling to protect patients and health care workers from unintentional radiation exposure. ( 2.1 , 5.2 ) 5.1 Risk of Image Misinterpretation Image interpretation errors can occur with POSLUMA PET. A negative image does not rule out the presence of prostate cancer and a positive image does not confirm the presence of prostate cancer. The performance of POSLUMA for imaging metastatic pelvic lymph nodes in patients prior to initial definitive therapy seems to be affected by serum PSA levels and risk grouping [See Clinical Studies ( 14.1 )] . The performance of POSLUMA for imaging patients with biochemical evidence of recurrence of prostate cancer seems to be affected by serum PSA levels [See Clinical Studies ( 14.2 )] . Flotufolastat F 18 uptake is not specific for prostate cancer and may occur in other types of cancer, in non-malignant processes, and in normal tissues. Clinical correlation, which may include histopathological evaluation, is recommended. Risk of Image Misinterpretation in Patients with Suspected Prostate Cancer Recurrence The interpretation of POSLUMA PET may differ depending on imaging readers, particularly in the prostate/prostate bed region [see Clinical Studies ( 14.2 )]. Because of the associated risk of false positive interpretation, consider multidisciplinary consultation and histopathological confirmation when clinical decision-making hinges on flotufolastat F18 uptake only in the prostate/prostate bed region or only on uptake interpreted as borderline. 5.2 Radiation Risks POSLUMA use contributes to a patient's overall long-term cumulative radiation exposure. Long-term cumulative radiation exposure is associated with an increased risk for cancer. Advise patients to hydrate before and after administration and to void frequently after administration. Ensure safe handling to minimize radiation exposure to the patient and health care providers [see Dosage and Administration ( 2.1 , 2.2 )] .

7 DRUG INTERACTIONS Androgen deprivation therapy (ADT) and other therapies targeting the androgen pathway, such as androgen receptor antagonists, can result in changes in uptake of flotufolastat F 18 in prostate cancer. The effect of these therapies on performance of POSLUMA PET has not been established.

6 ADVERSE REACTIONS The most common adverse reactions (≥0.4%) are diarrhea, blood pressure increase, and injection site pain. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Blue Earth Diagnostics Ltd at 1-844-POSLUMA (1-844-767-5862) 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 POSLUMA was evaluated in 747 patients with prostate cancer [see Clinical Studies ( 14.1 , 14.2 )] . All patients received a single administration of POSLUMA with an administered radioactivity (mean ± SD) of 307 ± 23 MBq (8.3 ± 0.6 mCi). The mean age of patients was 67 years (range: 43 to 86 years); distribution by race was 78% White, 12% Black or African American, 2% other, and 7% unreported; and distribution by ethnicity was 5% Hispanic/Latino, 87% non-Hispanic/Latino, and 8% unreported. The adverse reactions reported in ≥ 0.4% of patients are shown in Table 2 . Table 2: Adverse Reactions in ≥ 0.4% of Patients with Prostate Cancer Receiving POSLUMA Adverse Reaction POSLUMA N = 747 n (%) Diarrhea 5 (0.7%) Blood pressure increase 4 (0.5%) Injection site pain 3 (0.4%)

8.1 Pregnancy Risk Summary POSLUMA is not indicated for use in females. There are no available data on the use of POSLUMA 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 flotufolastat F 18. Radioactive drugs, including POSLUMA, have the potential to cause fetal harm depending on the fetal stage of development and the magnitude of the radiation dose.