Copper Cu 64 Dotatate

Detectnet is indicated for use with positron emission tomography (PET) for localization of somatostatin receptor positive neuroendocrine tumors (NETs) in adult patients. Detectnet is a radioactive diagnostic agent indicated for use with positron emission tomography (PET) for localization of somatostatin receptor positive neuroendocrine tumors (NETs) in adult patients. ( 1 )

Injection; sterile, clear, colorless to yellow solution in a single-dose vial containing 148 MBq (4 mCi) (37 MBq (1 mCi) per 1 mL) of copper Cu 64 dotatate at calibration date and time. Injection: 148 MBq (4 mCi) (37 MBq (1 mCi) per 1 mL) of copper Cu 64 dotatate in a single-dose vial.( 3 )

None. None ( 4 ).

Radiation Risk: Ensure safe handling and preparation procedures to protect patients and health care workers from unintentional radiation exposure ( 5.1 ). Advise patients to hydrate before and after administration and to void frequently after administration. ( 2.3 ) Hypersensitivity Reactions: Most reported reactions were rash and pruritus and reversible either spontaneously or with routine symptomatic management. ( 5.2 ) Risk for Image Misinterpretation: Uptake of Detectnet can be seen in a variety of tumor types other than NETs, in other pathologic conditions, and as a normal physiologic variant (e.g., uncinate process of the pancreas). ( 5.3 )

5.1 Radiation Risk Diagnostic radiopharmaceuticals, including Detectnet, contribute to a patient’s overall long-term cumulative radiation exposure. Long-term cumulative radiation exposure is associated with an increased risk of cancer. Ensure safe handling and preparation procedures to protect patients and health care workers from unintentional radiation exposure. Advise patients to hydrate before and after administration and to void frequently after administration [see Dosage and Administration ( 2.1 , 2.3 )] .

5.2 Hypersensitivity Reactions Hypersensitivity reactions following administration of somatostatin receptor imaging agents predominantly consisted of cutaneous reactions such as rash and pruritus. Reactions reversed either spontaneously or with routine symptomatic management. Less frequently hypersensitivity reactions included angioedema or cases with features of anaphylaxis.

5.3 Risk for Image Misinterpretation The uptake of copper Cu 64 dotatate reflects the level of somatostatin receptor density in NETs, however, uptake can also be seen in a variety of other tumors that also express somatostatin receptors. Increased uptake might also be seen in other non-cancerous pathologic conditions that express somatostatin receptors including thyroid disease or in subacute inflammation, or might occur as a normal physiologic variant (e.g. uncinate process of the pancreas) [see Dosage and Administration ( 2.5 )] . A negative scan after the administration of Detectnet in patients who do not have a history of NET disease does not rule out disease [see Clinical Studies ( 14 )] .

The following clinically significant adverse reactions are described elsewhere in the labeling: Hypersensitivity reactions [see Warnings and Precautions ( 5.2 )] Reported adverse reactions include nausea, vomiting, and flushing. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact CURIUM US LLC at 1-866-789-2211 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. In safety and efficacy trials, 71 subjects received a single dose of Detectnet. Of these 71 subjects, 21 were healthy volunteers and the remainder were patients with known or suspected NET. The following adverse reactions occurred at a rate of < 2%: Gastrointestinal Disorders : nausea, vomiting Vascular Disorders : flushing In published clinical experience, 126 patients with known history of NET received a single dose of copper Cu 64 dotatate injection. Four patients were reported to have experienced nausea immediately after injection.

6.2 Postmarketing Experience The following adverse reactions have been identified during postapproval use of other somatostatin receptor imaging agents. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to the drug. Immune System Disorders: Hypersensitivity reactions, predominantly rash, pruritus, less frequently angioedema or features of anaphylaxis

Somatostatin Analogs: Somatostatin analogs competitively bind to the same somatostatin receptors as copper Cu 64 dotatate and may affect imaging. Image patients just prior to dosing with somatostatin analogs. For patients on long-acting somatostatin analogs, a wash-out period of 28 days is recommended prior to imaging. For patients on short-acting somatostatin analogs, a washout period of 2 days is recommended prior to imaging. ( 2.3 , 7.1 )

7.1 Somatostatin Analogs Non-radioactive somatostatin analogs and copper Cu 64 dotatate competitively bind to somatostatin receptors (SSTR2). Image patients just prior to dosing with somatostatin analogs. For patients on long-acting somatostatin analogs, a wash-out period of 28 days is recommended prior to imaging. For patients on short-acting somatostatin analogs, a washout period of 2 days is recommended prior to imaging [see Dosage and Administration ( 2.3 )].

Lactation: Advise patients to interrupt breastfeeding for 12 hours after Detectnet administration. ( 8.2 )

8.1 Pregnancy Risk Summary All radiopharmaceuticals, including Detectnet have the potential to cause fetal harm depending on the fetal stage of development and the magnitude of the radiation dose. Advise a pregnant woman of the potential risks of fetal exposure to radiation from administration of Detectnet. There are no data on Detectnet use in pregnant women to evaluate for a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes. No animal reproduction studies have been conducted with copper Cu 64 dotatate injection. The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. 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% to 4% and 15% to 20%, respectively.

8.2 Lactation Risk Summary There are no data on the presence of copper Cu 64 dotatate in human milk, the effect on the breastfed infant, or the effect on milk production. Lactation studies have not been conducted in animals. Advise a lactating woman to interrupt breastfeeding for 12 hours after Detectnet administration in order to minimize radiation exposure to a breastfed infant.

8.4 Pediatric Use The safety and effectiveness of Detectnet have not been established in pediatric patients.

8.5 Geriatric Use Clinical studies of Detectnet did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.

Copper Cu 64 dotatate binds to somatostatin receptors with highest affinity for subtype 2 receptors (SSTR2). It binds to cells that express somatostatin receptors including malignant neuroendocrine cells, which overexpress SSTR2 receptors. Copper Cu 64 is a positron (β + ) emitting radionuclide with an emission yield that allows positron emission tomography (PET) imaging.