Gozellix

1 INDICATIONS AND USAGE GOZELLIX, after radiolabeling with Ga 68, 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. GOZELLIX, after radiolabeling with Ga 68, 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 Use appropriate aseptic technique and radiation safety handling measures in the manipulation and administration of Gallium Ga 68 Gozetotide Injection. ( 2.1 ) The recommended amount of radioactivity for adults is 111 MBq to 259 MBq (3 mCi to 7 mCi) as a bolus intravenous injection. ( 2.2 ) A diuretic expected to act within the uptake time period may be administered at the time of radiotracer injection. ( 2.2 ) Initiate imaging 50 minutes to 100 minutes after administration. The patient should void immediately prior to initiation of imaging. The scan should begin caudally and proceed cranially. ( 2.10 ) See full prescribing information for additional preparation, administration, imaging, and radiation dosimetry information. ( 2 ) 2.1 Radiation Safety - Drug Handling After radiolabeling of GOZELLIX, the vial contains Gallium Ga 68 Gozetotide Injection. Handle Gallium Ga 68 Gozetotide Injection with appropriate safety measures to minimize radiation exposure [see Warnings and Precautions (5.2) ] . Use waterproof gloves, effective radiation shielding, and other appropriate safety measures when preparing and handling Gallium Ga 68 Gozetotide Injection. Radiopharmaceuticals should be used by or under the control of healthcare providers 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 Dosage and Administration Instructions Recommended Dosage In adults, the recommended amount of radioactivity to be administered for PET is 111 MBq to 259 MBq (3 mCi to 7 mCi) administered as an intravenous bolus injection. Administration Use aseptic technique and radiation shielding when withdrawing and administering Gallium Ga 68 Gozetotide Injection. Calculate the necessary volume to administer based on calibration time and required dose. Inspect Gallium Ga 68 Gozetotide Injection visually for particulate matter and discoloration before administration. Only use solutions that are clear, colorless to slightly yellow, and without visible particles. Assay the final dose in a dose calibrator immediately before administration to the patient. After injection of Gallium Ga 68 Gozetotide Injection, administer an intravenous flush of sterile 0.9% Sodium Chloride Injection to ensure full delivery of the dose. Dispose of any unused drug in a safe manner in compliance with applicable regulations. Unless contraindicated, a diuretic expected to act within the uptake time period may be administered at the time of radiotracer injection to potentially decrease artifact from radiotracer accumulation in the urinary bladder and ureters. 2.3 Patient Preparation Instruct patients to drink a sufficient amount of water to ensure adequate hydration prior to administration of Gallium Ga 68 Gozetotide Injection and to continue to drink and void frequently following administration to reduce radiation exposure, particularly during the first hour after administration [see Warnings and Precautions (5.2) ] . 2.4 General Instructions for Drug Preparation Ga 68 Sources and GOZELLIX Carton Configurations GOZELLIX is supplied as a kit in two different carton configurations, A or B, for preparation of Gallium Ga 68 Gozetotide Injection with eluate from different Ga 68 sources. See Table 1 for GOZELLIX carton configurations to be used with different Ga 68 sources. Table 1. Ga 68 Sources and GOZELLIX Carton Configuration Ga 68 Source GOZELLIX Carton Configuration to be Used Cyclotron-produced via GE FASTlab A Cyclotron-produced via Alternative Radioisotope Technologies for Medical Science (ARTMS) QUANTM Irradiation System (QIS) A Eckert & Ziegler (EZAG) GalliaPharm Germanium 68/Gallium 68 (Ge 68/Ga 68) generator A IRE ELiT Galli Eo Ge 68/Ga 68 generator B The Ge 68/Ga 68 generators and cyclotron are not supplied with GOZELLIX. Follow the instructions for use provided by the Ge 68/Ga 68 generator or cyclotron manufacturer. Components of GOZELLIX consist of Vial 1 (Gozetotide), Vial 2A or Vial 2B (Acetate Buffer), and an Ampule (Ascorbic Acid Stabilizer) [see How Supplied/Storage and Handling (16) ] . General Instructions Follow aseptic techniques in all drug preparation and handling. Use suitable shielding to reduce radiation exposure. Wear waterproof gloves. Place a "radioactive" label on Vial 1 (Gozetotide) with product name, lot number and date. Remove the vial cap from Vial 1 (Gozetotide) and Vial 2A or Vial 2B (Acetate Buffer). Swab the top of each vial and the outside of the ampule with alcohol to disinfect the surface and allow the top of each vial to dry. Use the shortest possible needle for the transfer of the Gallium Ga 68 Chloride solution to minimize any potential metallic contamination. The needle should be clean and dilute acid resistant. Use only plastic syringes for preparation and administration. Do not use syringes with rubber plungers. Prior to use of any vial, confirm the correct vial by a visual check of the vial label. Prepare the acetate buffer by adding 0.10 mL ascorbic acid stabilizer according to the instruction below before proceeding with the specific procedure depending on Ga 68 source. Follow the specific preparation procedure dependent on Ga 68 source [see Dosage and Administration (2.5 , 2.6 , 2.7 , 2.8) ] . Procedure for Addition of Ascorbic Acid Stabilizer to Acetate Buffer Safely open the ascorbic acid stabilizer ampule. Using an appropriately sized syringe (e.g., 0.5 mL syringe) fitted with a 5 micron 18 G × 1 1/2 inch sterile filter needle or equivalent, withdraw the solution of ascorbic acid, through the filter needle. NOTE: The syringe must contain at least 0.10 mL of ascorbic acid stabilizer solution that can then be dispensed. The operator must account for the dead volume of the syringe and filter needle. Remove the filter needle from the syringe and fit a sterile needle to the syringe containing the ascorbic acid. Dispense 0.10 mL of the ascorbic acid stabilizer solution from the syringe into the acetate buffer vial (Vial 2A or Vial 2B). After removal of the syringe from the vial, mix the contents by inverting the vial at least three times. 2.5 Preparation with Cyclotron-Produced Ga 68 via GE FASTlab Solid or Liquid Target System Collection of Gallium Ga 68 Chloride Solution After purification by the FASTlab, the Gallium Ga 68 Chloride solution is passed through a sterile filter and into the cassette product vial automatically by the FASTlab. When Ga 68 is cyclotron-produced, test for Ga 66 and Ga 67 (with specification of ≤2% combined total) when a new lot of Zn 68 is introduced for manufacturing. Radiolabeling Procedure Use GOZELLIX "Configuration A" with cyclotron-produced Ga 68 via GE FASTlab Solid or Liquid Target System. A schematic diagram for the preparation is provided in Figure 1. Prepare the acetate buffer (Vial 2A) with ascorbic acid stabilizer as outlined in the procedure above [see Dosage and Administration (2.4) ] . Pierce Vial 1 (Gozetotide) with a sterile needle connected to a 0.2 micron sterile vented filter to maintain atmospheric pressure within the vial during the reconstitution process. Insert a sterile syringe with a needle into Vial 2A containing the acetate and ascorbic acid buffer solution and draw up 2.6 mL of the solution. Aseptically transfer the acetate and ascorbic acid buffer solution in the syringe into Vial 1 (Gozetotide). Gently swirl Vial 1 to ensure the product is thoroughly dissolved in the buffer. Aseptically transfer the 5 mL of Gallium Ga 68 Chloride solution made using the GE FASTlab Solid or Liquid Target System into Vial 1 (Gozetotide). Remove the sterile vent filter. Gently swirl Vial 1 to ensure the product is thoroughly mixed. Wait for 5 minutes for radiolabeling to take place at room temperature (25°C (77°F); excursions permitted to 15°C to 30°C (59°F to 86°F)). Assay the whole vial containing the Gallium Ga 68 Gozetotide Injection for total radioactivity using a dose calibrator, calculate the radioactivity concentration, and record the result. Dilute the Gallium Ga 68 Gozetotide Injection with 2.4 mL of 0.9% Sodium Chloride Injection to a final volume of 10 mL. Perform the quality control of Gallium Ga 68 Gozetotide Injection according to the recommended methods [see Dosage and Administration (2.9) ] . Prior to use, visually inspect the solution behind a shielded screen for radioprotection purposes. Only use solutions that are clear without visible particles. Keep the vial containing the Gallium Ga 68 Gozetotide Injection upright in a radioprotective shield container at room temperature until use. The final volume of the Gallium Ga 68 Gozetotide Injection is 10 mL after dilution with 0.9% Sodium Chloride Injection. Use within 4 hours if preparation contains less than 2,590 MBq (70 mCi) or within 6 hours if preparation contains 2,590 MBq to 18,500 MBq (70 mCi to 500 mCi) . Figure 1: Drug Preparation with Cyclotron-Produced Ga 68 via GE FASTlab Solid or Liquid Target System Figure 1 2.6 Preparation with Cyclotron-Produced Ga 68 via ARTMS QIS Solid Target System Collection of Gallium Ga 68 Chloride Solution After purification by the ARTMS QIS, the Gallium Ga 68 Chloride solution is passed through a sterile filter and into the cassette product vial automatically by the ARTMS QIS. When Ga 68 is cyclotron-produced, test for Ga 66 and Ga 67 (with specification of ≤2% combined total) when a new lot of Zn 68 is introduced for manufacturing. Radiolabeling Procedure Use GOZELLIX "Configuration A" with cyclotron-produced Ga 68 via ARTMS QIS Solid Target System. A schematic diagram for the preparation is provided in Figure 2. Prepare the acetate buffer (Vial 2A) with ascorbic acid stabilizer as outlined in the procedure above [see Dosage and Administration (2.4) ] . Pierce Vial 1 (Gozetotide) with a sterile needle connected to a 0.2 micron sterile vented filter to maintain atmospheric pressure within the vial during the reconstitution process. Insert a sterile syringe with a needle into Vial 2A containing the acetate and ascorbic acid buffer solution and draw up 2.6 mL of the solution. Aseptically transfer the acetate and ascorbic acid buffer solution in the syringe into Vial 1 (Gozetotide). Gently swirl Vial 1 to ensure the product is thoroughly dissolved in the buffer. Aseptically transfer the 5 mL of Gallium Ga 68 Chloride solution made using the ARTMS QIS Solid Target System into Vial 1 (Gozetotide). Remove the sterile vent filter. Gently swirl Vial 1 to ensure the product is thoroughly mixed. Wait for 5 minutes for radiolabeling to take place at room temperature (25°C (77°F)); excursions permitted to 15°C to 30°C (59°F to 86°F)). Assay the whole vial containing the Gallium Ga 68 Gozetotide Injection for total radioactivity using a dose calibrator, calculate the radioactivity concentration, and record the result. Dilute the Gallium Ga 68 Gozetotide Injection with 2.4 mL of 0.9% Sodium Chloride Injection to a final volume of 10 mL. Perform the quality control of Gallium Ga 68 Gozetotide Injection according to the recommended methods [see Dosage and Administration (2.9) ] . Prior to use, visually inspect the solution behind a shielded screen for radioprotection purposes. Only use solutions that are clear without visible particles. Keep the vial containing the Gallium Ga 68 Gozetotide Injection upright in a radioprotective shield container at room temperature until use. The final volume of the Gallium Ga 68 Gozetotide Injection is 10 mL after dilution with 0.9% Sodium Chloride Injection. Use within 4 hours if preparation contains less than 2,590 MBq (70 mCi) or within 6 hours if preparation contains 2,590 MBq to 18,500 MBq (70 mCi to 500 mCi). Figure 2: Drug Preparation with Cyclotron-Produced Ga 68 via ARTMS QIS Solid Target System Figure 2 2.7 Preparation with EZAG GalliaPharm Generator Follow the generator manufacturers' instructions for generator preparation, controls, and continuous routine elution. Radiolabeling Procedure Use GOZELLIX "Configuration A" with an EZAG GalliaPharm generator. A schematic diagram for the preparation is provided in Figure 3. Prepare the acetate buffer vial (Vial 2A) with ascorbic acid stabilizer as outlined in the procedure above [see Dosage and Administration (2.4) ] . Pierce Vial 1 (Gozetotide) with a sterile needle connected to a 0.2 micron sterile vented filter to maintain atmospheric pressure within the vial during the reconstitution process. Insert a sterile syringe with a needle into Vial 2A containing the acetate and ascorbic acid buffer solution and draw up 2.6 mL of the solution. Aseptically transfer the acetate and ascorbic acid buffer solution in the syringe into Vial 1 (Gozetotide). Gently swirl Vial 1 to ensure the product is thoroughly dissolved in the buffer. Prepare a syringe containing 5 mL of sterile ultrapure 0.1 M HCl provided with the GalliaPharm generator for elution. Connect the male luer of the outlet line of the GalliaPharm generator to a sterile needle. Connect Vial 1 containing the dissolved gozetotide solution directly to the outlet line of the GalliaPharm generator by pushing the needle through the rubber septum and place the vial in a radiation shielded container. Ensure the vent needle and needle to the generator outlet are pulled up as far as possible to not contact the solution in the vial. Elute the generator directly with the 5 mL 0.1 M HCl from step 8 into Vial 1 according to the instructions for use of the GalliaPharm generator that are supplied by EZAG. At the end of the elution, disconnect the generator from Vial 1 by removing the needle from the rubber septum and remove the sterile vent filter. Gently swirl the vial to ensure the product is thoroughly mixed. Wait for 5 minutes for radiolabeling to take place at room temperature (25°C (77°F); excursions permitted to 15°C to 30°C (59°F to 86°F)). Assay the whole vial containing the Gallium Ga 68 Gozetotide Injection for total radioactivity using a dose calibrator, calculate the radioactivity concentration, and record the result. Dilute the Gallium Ga 68 Gozetotide Injection with 2.4 mL of 0.9% Sodium Chloride Injection to a final volume of 10 mL. Perform the quality control of Gallium Ga 68 Gozetotide Injection according to the recommended methods [see Dosage and Administration (2.9) ] . Prior to use, visually inspect the solution behind a shielded screen for radioprotection purposes. Only use solutions that are clear without visible particles. Keep the vial containing the Gallium Ga 68 Gozetotide Injection upright in a radioprotective shield container at room temperature until use. The final volume of the Gallium Ga 68 Gozetotide Injection is 10 mL after dilution with 0.9% Sodium Chloride Injection. Use within 4 hours if preparation contains less than 2,590 MBq (70 mCi) or within 6 hours if preparation contains 2,590 MBq to 18,500 MBq (70 mCi to 500 mCi). Figure 3: Preparation with EZAG GalliaPharm Generator Figure 3 2.8 Preparation with IRE ELiT Galli Eo Generator Follow the generator manufacturers' instructions for generator preparation, controls, and continuous routine elution. Radiolabeling Procedure Use GOZELLIX "Configuration B" with an IRE EliT Galli Eo generator. A schematic diagram for the preparation is provided in Figure 4. Prepare the acetate buffer vial (Vial 2B) with ascorbic acid stabilizer as outlined in the procedure above [see Dosage and Administration (2.4) ] . Pierce Vial 1 (Gozetotide) with a sterile needle connected to a 0.2 micron sterile vented filter to maintain atmospheric pressure within the vial during the reconstitution process. Insert a sterile syringe with a needle into Vial 2B containing the acetate and ascorbic acid buffer solution and draw up 6.5 mL of the solution. Aseptically transfer the acetate and ascorbic acid buffer solution in the syringe into Vial 1 (Gozetotide). Gently swirl Vial 1 to ensure the product is thoroughly dissolved in the buffer. Remove the 0.2 micron sterile vented filter from Vial 1. Connect the male luer of the outlet line of the Galli Eo generator to a sterile needle. Connect Vial 1 containing the dissolved gozetotide solution directly to the outlet line of the Galli Eo generator by pushing the needle through the vial's septum. Ensure the needle to the generator outlet is pulled up as far as possible to not contact the solution in the vial. Elute 1.1 mL from the generator directly into Vial 1 (Gozetotide) according to the instructions for use of the Galli Eo generator that are supplied by IRE that describe elution into a non-evacuated vial. At the end of the elution, disconnect the generator from Vial 1 by removing the needle from the rubber septum. Gently swirl Vial 1 to ensure the product is thoroughly mixed. Wait for 5 minutes for radiolabeling to take place at room temperature (25°C (77°F); excursions permitted to 15°C to 30°C (59°F to 86°F)). Assay the whole vial containing the Gallium 68 Gozetotide Injection for total radioactivity using a dose calibrator, calculate the radioactivity concentration, and record the result. Dilute the Gallium Ga 68 Gozetotide Injection with 2.4 mL of 0.9% Sodium Chloride Injection to a final volume of 10 mL. Perform the quality control of Gallium Ga 68 Gozetotide Injection according to the recommended methods [see Dosage and Administration (2.9) ] . Prior to use, visually inspect the solution behind a shielded screen for radioprotection purposes. Only use solutions that are clear without visible particles. Keep the vial containing the Gallium Ga 68 Gozetotide Injection upright in a radioprotective shield container at room temperature until use. The final volume of the Gallium Ga 68 Gozetotide Injection is 10 mL after dilution with 0.9% Sodium Chloride Injection. Use within 4 hours if preparation contains less than 2,590 MBq (70 mCi) or within 6 hours if preparation contains 2,590 MBq to 18,500 MBq (70 mCi to 500 mCi). Figure 4: Preparation with IRE ELiT Galli Eo Generator Figure 4 2.9 Specifications and Quality Control Perform the quality controls in Table 2 behind a lead glass shield for radioprotection purposes. Table 2: Specifications for Gallium Ga 68 Gozetotide Injection Test Analytical method Acceptance criteria Appearance Visual examination Colorless to slightly yellow solution Free from visible particles pH pH-meter or pH-strips 4.0 to 5.0 Radiochemical purity Instant thin-layer chromatography, silica gel (iTLC SG); See methods below Content of gallium Ga 68 gozetotide Content of free and colloidal Ga 68 ≥95% ≤5% Procedure for instant Thin Layer Chromatography (iTLC) Pour ammonium acetate 1 M/methanol (1/1 v/v) solution to a depth of 3 mm to 4 mm in the developing chamber, cover the chamber and allow it to equilibrate. Prepare an iTLC strip that is 12 cm in length approximately 2.5 cm in width. Using a pencil and ruler, carefully draw a solid line at least 1 cm from the bottom of the iTLC strip. Using a pencil and ruler, carefully draw a solid line 10 cm above the pencil line drawn in Step 3. Using a pencil and ruler, draw a dotted line 2 cm above the solid line at the bottom of the iTLC strip. Using a pencil and ruler, draw a second dotted line 6 cm above the solid line at the bottom of the iTLC strip. Mark the section below this line with an "X". See Figure 5 for an example of how to mark the iTLC strip. Apply a drop of gallium Ga 68 gozetotide solution into the center of the solid line at 1 cm from the bottom of the TLC plate. Place the iTLC strip into the development chamber, with the bottom of the iTLC strip containing drop of gallium Ga 68 gozetotide into the solution at the bottom of the developing chamber. Ensure that the bottom of the iTLC strip sits in the liquid in the chamber, but that the liquid does not touch the drop of gallium Ga 68 gozetotide. Allow the iTLC strip to develop in the covered chamber over a distance of 10 cm from the point of application (until the solvent reaches the solid line near the top of the iTLC strip). Remove the iTLC strip. Allow the plate to dry before proceeding with analysis using one of the methods described below. Perform one of the following: Radiochemical Purity Analysis Using Cutting Technique Cut the iTLC strip into 3 parts by cutting horizontally at the dotted line 2 cm above the solid line at the bottom of the iTLC strip and the dotted line 6 cm above the solid line at the bottom of the iTLC strip. See Figure 5 for where to cut the iTLC strip. This cutting will result in the following 3 portions: A 3 cm portion containing the Origin and free/colloidal Ga 68 species (Bottom Portion) A 4 cm portion marked with an "X" containing no sample (this portion is NOT measured) A 5 cm portion containing the solvent front and gallium Ga 68 gozetotide (Top Portion) Using a dose calibrator or gamma spectrometer, measure and record the radioactivity in the 3 cm portion of the cut TLC plate that contains the Origin and free/colloidal Ga 68 species (Bottom Portion). Using a dose calibrator or gamma spectrometer, measure and record the radioactivity in the 5 cm portion containing the solvent front and gallium Ga 68 gozetotide (Top Portion). Calculate the quantity (in percent) of gallium Ga 68 gozetotide in the solution using the formula: Radiochemical Purity (%) = Counts Top Portion × 100 Counts from Top Portion + Counts from Bottom Portion Figure 5: iTLC Strip Preparation and Cutting Points for the Cutting Technique Figure 5 Radiochemical Purity Analysis Using Scanning Technique Scan the iTLC strip with a radiometric iTLC scanner. Calculate the quantity (in percent) of gallium Ga 68 gozetotide in the solution by integration of the peaks on the chromatogram. The retention factor (Rf) specifications are: Free and colloidal Ga 68 species, Rf = 0 to 0.1, Gallium Ga 68 gozetotide, Rf = 0.6 to 1. 2.10 Image Acquisition Position the patient supine with arms above the head. Begin PET scanning 50 minutes to 100 minutes after the intravenous administration of Gallium Ga 68 Gozetotide Injection. Patients should void immediately prior to image acquisition and image acquisition should begin at the proximal thighs and proceed cranially to the skull base or skull vertex. Adapt imaging technique according to the equipment used and patient characteristics in order to obtain the best image quality possible. 2.11 Image Interpretation Gallium Ga 68 gozetotide binds to PSMA. Based on the intensity of the signals, PET images obtained using gallium Ga 68 gozetotide indicate the presence of PSMA in tissues. 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) ] . 2.12 Radiation Dosimetry Estimated radiation absorbed doses per injected activity for organs and tissues of adult male patients following an intravenous bolus of Gallium Ga 68 Gozetotide Injection are shown in Table 3. The effective radiation dose resulting from the administration of the maximum recommended activity of 259 MBq (7 mCi) is about 4.4 mSv. The radiation doses for this administered activity to the critical organs, which are the kidneys, urinary bladder, and spleen, are 96.2 mGy, 25.4 mGy, and 16.8 mGy, respectively. These radiation doses are for Gallium Ga 68 Gozetotide Injection alone. If CT or a transmission source are used for attenuation correction, the radiation dose will increase by an amount that varies by technique. Table 3: Estimated Radiation Absorbed Dose per Injected Activity in Selected Organs and Tissues of Adults after Intravenous Administration of Gallium Ga 68 Gozetotide Injection Organ Absorbed dose (mGy/MBq) Mean SD Adrenals 0.0156 0.0014 Brain 0.0104 0.0011 Breasts 0.0103 0.0011 Gallbladder 0.0157 0.0012 Lower Colon 0.0134 0.0009 Small Intestine 0.014 0.002 Stomach 0.0129 0.0008 Heart 0.012 0.0009 Kidneys 0.3714 0.0922 Liver 0.0409 0.0076 Lungs 0.0111 0.0007 Muscle 0.0103 0.0003 Pancreas 0.0147 0.0009 Red Marrow 0.0114 0.0016 Skin 0.0091 0.0003 Spleen 0.065 0.018 Testes 0.0111 0.0006 Thymus 0.0105 0.0006 Thyroid 0.0104 0.0006 Urinary Bladder 0.0982 0.0286 Total Body 0.0143 0.0013 Effective Dose (mSv/MBq) 0.0169 0.0015

4 CONTRAINDICATIONS None None ( 4 )

5 WARNINGS AND PRECAUTIONS Risk for Misinterpretation: Gallium Ga 68 gozetotide uptake can be seen in a variety of tumor types and in non-malignant processes. Clinical correlation, which may include histopathological evaluation of the suspected prostate cancer site, is recommended. ( 5.1 ) Radiation Risks: Ensure safe handling to protect patients and health care providers from unintentional radiation exposure. ( 2.1 , 5.2 ) Hypersensitivity Reactions to Sulfites: Ascorbic Acid Stabilizer contains sodium metabisulfite, a sulfite that may cause life-threatening hypersensitivity reactions including anaphylaxis. ( 5.3 ) 5.1 Risk for Misinterpretation Image interpretation errors can occur with GOZELLIX 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. Gallium Ga 68 gozetotide uptake is not specific for prostate cancer and may occur with other types of cancer as well as non-malignant processes such as Paget's disease, fibrous dysplasia, and osteophytosis. The performance of GOZELLIX for imaging of biochemically recurrent prostate cancer seems to be affected by serum PSA levels and by site of disease. The performance of GOZELLIX for imaging of metastatic pelvic lymph nodes prior to initial definitive therapy seems to be affected by Gleason score [ see Clinical Studies (14.1 , 14.2) ] . Clinical correlation, which may include histopathological evaluation of the suspected prostate cancer site, is recommended. 5.2 Radiation Risks Gallium Ga 68 gozetotide contributes to a patient's overall long-term cumulative radiation exposure. Long-term cumulative radiation exposure is associated with an increased risk for cancer. Ensure safe handling to minimize radiation exposure to the patient and health care providers. Advise patients to hydrate before and after administration and to void frequently after administration [see Dosage and Administration (2.1 , 2.3) ] . 5.3 Hypersensitivity Reactions to Sulfites Ascorbic Acid Stabilizer contains sodium metabisulfite, a sulfite that may cause allergic-type reactions including anaphylactic symptoms and life-threatening or less severe asthmatic episodes in certain susceptible people. The overall prevalence of sulfite sensitivity in the general population is unknown and probably low. Sulfite sensitivity is seen more frequently in asthmatic than in non-asthmatic people.

7 DRUG INTERACTIONS Androgen deprivation therapy and other therapies targeting the androgen pathway Androgen deprivation therapy (ADT) and other therapies targeting the androgen pathway, such as androgen receptor antagonists, can result in changes in uptake of gallium Ga 68 gozetotide in prostate cancer. The effect of these therapies on performance of gallium Ga 68 gozetotide PET has not been established.

6 ADVERSE REACTIONS The most commonly reported adverse reactions include nausea, diarrhea, and dizziness. ( 6 ) To report SUSPECTED ADVERSE REACTIONS, contact Telix Pharmaceuticals (US) Inc. at 1-844-455-8638 or contact FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 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 GOZELLIX has been established based on two prospective studies of another formulation of gallium Ga 68 gozetotide in patients with prostate cancer [see Clinical Studies (14.1 , 14.2) ] . Below is a display of the adverse reactions in these studies. The safety of gallium Ga 68 gozetotide was evaluated in 960 patients in the PSMA-PreRP and PSMA-BCR studies, each receiving one dose of gallium Ga 68 gozetotide. The average injected activity was 188.7 ± 40.7 MBq (5.1 ± 1.1 mCi) [see Clinical Studies (14.1 , 14.2) ] . The most commonly reported adverse reactions were nausea, diarrhea, and dizziness, occurring at a rate of <1%.

8.1 Pregnancy Risk Summary GOZELLIX is not indicated for use in females. There are no available data with gallium Ga 68 gozetotide injection use in pregnant women to evaluate for a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes. All radiopharmaceuticals, including GOZELLIX, have the potential to cause fetal harm depending on the fetal stage of development and the magnitude of the radiation dose. Animal reproduction studies have not been conducted with gallium Ga 68 gozetotide.