FDA label 32c5e2b4-e96e-4e94-bcf6-e4b0cf6840f4

5 WARNINGS AND PRECAUTIONS Risk for Misinterpretation: Gallium Ga 68 gozetotide uptake may occur in other tumor types and in non-malignant processes. Interpretation of LOCAMETZ PET imaging with histopathology and/or other diagnostic procedures is recommended. ( 5.1 ) Radiation Risk: Gallium Ga 68 gozetotide contributes to a patient’s overall long-term cumulative radiation exposure. Ensure safe handling and preparation procedures to protect patients and health care workers from unintentional radiation exposure. ( 5.2 ) 5.1 Risk for Misinterpretation Image interpretation errors can occur with LOCAMETZ PET. Negative imaging does not rule out the presence of prostate cancer and positive imaging 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. Clinical correlation, which may include histopathological evaluation of the suspected prostate cancer site, is recommended. The performance of LOCAMETZ for imaging of biochemically recurrent prostate cancer seems to be affected by serum PSA levels and by site of disease. The performance of LOCAMETZ 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)] . 5.2 Radiation Risk Gallium Ga 68 gozetotide contributes to the patient’s overall long-term cumulative radiation exposure. Long-term cumulative radiation exposure is associated with an increased risk of cancer. Ensure safe handling to minimize radiation exposure to the patient and health care workers. Advise patients to be well hydrated prior to gallium Ga 68 gozetotide injection administration and to void immediately prior to and frequently during the first hours after image acquisition to reduce radiation exposure [see Dosage and Administration (2.1, 2.3)] .

6 ADVERSE REACTIONS The adverse reactions (incidence ≥ 0.5%) are fatigue, nausea, constipation, and vomiting. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Novartis Pharmaceuticals Corporation at 1-888-669-6682 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 LOCAMETZ has been established based on three prospective studies of gallium Ga 68 gozetotide in patients with prostate cancer (i.e., Studies 1, 2, and 3). Adverse reactions from these studies are reported below. In Studies 1 and 2 using another formulation of gallium Ga 68 gozetotide injection, 960 patients received one dose of gallium Ga 68 gozetotide intravenously with the amount (mean ± SD) of radioactivity 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%. In a randomized, multicenter, open-label clinical study (NCT03511664, referred to as Study 3) in which gallium Ga 68 gozetotide was used to identify PSMA-positive patients on PET imaging to determine eligibility for PSMA-directed therapy, 1,003 patients with progressive metastatic castration-resistant prostate cancer (mCRPC) received one dose of gallium Ga 68 gozetotide intravenously with the amount of radioactivity 167.1 ± 23.1 MBq (4.52 ± 0.62 mCi). Patients were males with median age of 70 years (range, 40 to 94 years), were White (87%), Black or African American (7%), or Asian (2.4%), and had median baseline PSA levels of 74 ng/mL (range, 0 to 8995 ng/mL). Adverse reactions occurring at ≥ 0.5% in patients with metastatic prostate cancer who received gallium Ga 68 gozetotide injection in Study 3 are presented in Table 3. Table 3. Adverse Reactions (≥ 0.5%) in Patients with Metastatic Prostate Cancer Who Received Gallium Ga 68 Gozetotide Injection in Study 3 Adverse reactions Gallium Ga 68 Gozetotide Injection N = 1003 n (%) General disorders Fatigue 12 (1.2) Gastrointestinal disorders Nausea 8 (0.8) Constipation 5 (0.5) Vomiting 5 (0.5) Adverse reactions occurring at a rate of < 0.5% in the study were diarrhea, dry mouth, injection site reactions including injection site hematoma and injection site warmth, and chills.

<table width="50%"><caption>Table 3. Adverse Reactions (&#x2265; 0.5%) in Patients with Metastatic Prostate Cancer Who Received Gallium Ga 68 Gozetotide Injection in Study 3</caption><col width="50%"/><col width="50%"/><tbody><tr><td styleCode="Lrule Rrule" valign="top"><content styleCode="bold">Adverse reactions</content></td><td styleCode="Lrule Rrule" align="center"><content styleCode="bold">Gallium Ga 68 Gozetotide Injection N = 1003 n (%)</content></td></tr><tr><td styleCode="Toprule Lrule Rrule " align="left" colspan="2"><content styleCode="bold">General disorders</content></td></tr><tr><td styleCode="Toprule Lrule Rrule">Fatigue</td><td styleCode="Toprule Lrule Rrule" align="center">12 (1.2) </td></tr><tr><td styleCode="Toprule Lrule Rrule " align="left" colspan="2"><content styleCode="bold">Gastrointestinal disorders</content></td></tr><tr><td styleCode="Toprule Lrule Rrule">Nausea</td><td styleCode="Toprule Lrule Rrule" align="center">8 (0.8)</td></tr><tr><td styleCode="Toprule Lrule Rrule">Constipation</td><td styleCode="Toprule Lrule Rrule" align="center">5 (0.5)</td></tr><tr><td styleCode="Toprule Lrule Rrule">Vomiting</td><td styleCode="Toprule Lrule Rrule" align="center">5 (0.5)</td></tr></tbody></table>