Lutetium Lu 177 dotatate

Lutetium Lu 177 dotatate is used for: Indicated for somatostatin receptor-positive gastroenteropancreatic neuroendocrine tumors (GEP-NETs), including foregut, midgut, and hindgut neuroendocrine tumors in adults

Neuroendocrine Tumors Indicated for somatostatin receptor-positive gastroenteropancreatic neuroendocrine tumors (GEP-NETs), including foregut, midgut, and hindgut neuroendocrine tumors in adults 7.4 GBq (200 mCi) IV q8weeks for a total of 4 doses administered with premedication and concomitant medications Hepatic impairment Mild-to-moderate: No dose adjustment required Severe (TB >3 x ULN and any AST): Not studied

Renal impairment Mild-to-moderate (CrCl 30-70 mL/min): No dose adjustment required; however, patients may be at greater risk of toxicity; perform more frequent assessments of renal function Severe (CrCl <30 mL/min) or end-stage renal disease: Not studied

IV Preparation Use aseptic technique and radiation shielding when administering solution Use tongs when handling vial to minimize radiation exposure Do not inject directly into any other IV solution Confirm the amount of radioactivity in the radiopharmaceutical vial with an appropriate dose calibrator prior to and after administration Inspect the product visually for particulate matter and discoloration under a shielded screen prior to administration; solution should appear clear and colorless to slightly yellow; discard vial if particulates or discoloration are present Handling radiopharmaceuticals Radiopharmaceutical; handle with appropriate safety measures to minimize radiation exposure Use waterproof gloves and effective radiation shielding when handling 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, and whose experience and training have been approved by the appropriate governmental agency authorized to license the use of radiopharmaceuticals IV Administration Insert a 2.5-cm, 20-gauge needle (short needle) into the lutetium Lu 177-dota-tate vial and connect via a catheter to 500 mL 0.9% NaCl solution Ensure that the short needle does not touch the lutetium Lu 177-dota-tate solution in the vial and do not connect this short needle directly to the patient Do not allow 0.9% NaCl solution to flow into the lutetium Lu 177-dota-tate vial prior to the initiation of the infusion and do not inject lutetium Lu 177-dota-tate directly into the 0.9% NaCl solution Insert a second needle that is 9 cm, 18 gauge (long needle) into the lutetium Lu 177-dota-tate vial, ensuring that this long needle touches and is secured to the bottom of the vial during the entire infusion Connect the long needle to the patient by an IV catheter that is prefilled with 0.9% NaCl and that is used exclusively for the lutetium Lu 177-dota-tate infusion into the patient Use a clamp or pump to regulate the flow of the 0.9% NaCl solution via the short needle into the lutetium Lu 177-dota-tate vial at a rate of 50-100 mL/hr for 5-10 minutes and then 200-300 mL/hr for an additional 25-30 minutes The 0.9% NaCl solution entering the vial through the short needle will carry the lutetium Lu 177-dota-tate from the vial to the patient via the catheter connected to the long needle over a total duration of 30-40 minutes Do not administer lutetium Lu 177-dota-tate as an IV

Drug contributes to overall long-term radiation exposure; long-term cumulative radiation exposure is associated with an increased risk for cancer; radiation can be detected in the urine for up to 30 days; minimize radiation exposure to patients, medical personnel, and household contacts during and after treatment with institutional good radiation safety practices and patient management procedures Myelosuppression may occur; monitor blood cell counts Secondary myelodysplastic syndrome and leukemia reported Renal failure development may occur up to 36 mo after treatment; administer the recommended amino acid solution before, during, and after lutetium Lu 177-dota-tate to decrease reabsorption through the proximal tubules and decrease the radiation dose to the kidneys; patients with baseline renal impairment may be at greater risk Rare reports of hepatotoxicity; monitor transaminases, bilirubin, and serum albumin

Pregnancy Based on its mechanism of action, can cause fetal harm and infertility No data are available regarding use in pregnant women; however, all radiopharmaceuticals have the potential to cause fetal harm Advise pregnant women of the risk to a fetus Verify pregnancy status of females of reproductive potential prior to initiating Infertility May cause infertility in males and females The recommended cumulative dose of 29.6 GBq results in a radiation absorbed dose to the testis and ovaries within the range in which temporary or permanent infertility can be expected following external beam radiotherapy Contraception Females: Advise females of reproductive potential to use effective contraception during treatment and for 7 months after the final dose Males: Advise males with female partners of reproductive potential to use effective contraception during and for 4 months after the final dose Lactation There are no data on the presence of lutetium Lu 177 dotatate in human milk, or its effects on the breastfed infant or milk production No lactation studies in animals were conducted

Somatostatin and its analogs competitively bind to somatostatin receptors and may interfere with lutetium Lu 177-dota-tate efficacy

Side effects of Lutetium Lu 177 dotatate : >10% All Grades Lymphopenia (90%) Creatinine increased (85%) Hyperglycemia (82%) Anemia (81%) Increased GGT (66%) Increased alkaline phosphatase (65%) Nausea (65%) Leukopenia (55%) Vomiting (53%) Thrombocytopenia (53%) AST increased (50%) ALT increased (43%) Fatigue (38%) Hyperuricemia (34%) Hypocalcemia (32%) Blood bilirubin increased (30%) Hypokalemia (26%) Abdominal pain (26%) Diarrhea (26%) Neutropenia (26%) Decreased appetite (21%) Hyperkalemia (19%) Hypernatremia (17%) Headache (17%) Dizziness (17%) Peripheral edema (16%) Hypoglycemia (15%) Flushing (14%) Back pain (13%) Anxiety (12%) Renal failure (12%) Alopecia (12%) Hypertension (12%) Pain in extremity (11%) Cough (11%) >10% Grades 3-4 Lymphopenia (44%) Increased GGT (20%)

Radiolabeled somatostatin analog; binds to somatostatin receptors with highest affinity for subtype 2 receptors (SSRT2) Upon binding to somatostatin receptor-expressing cells, including malignant somatostatin receptor-positive tumors, the compound is internalized Beta emission from Lu 177 induces cellular damage by forming free radicals in somatostatin receptor-positive cells and in neighboring cells