Lutetium Lu 177-Dota-Tate

Lutetium Lu 177-dota-tate is used for somatostatin receptor-positive gastroenteropancreatic neuroendocrine tumors (GEP-NETs), including foregut, midgut, and hindgut neuroendocrine tumors in adults. Lutetium Lu 177- dota-tate is available under the following different brand names: Lutathera.

Dosages of Lutetium Lu 177-Dota-Tate:
Dosage Forms and Strengths
Injection, Solution for IV Use

• 370 MBq/mL (10 mCi/mL) single-dose vial
• Solution volume in each vial adjusted from 20.5-25 mL to provide a total of 7.4 GBq (200 mCi) of radioactivity per vial

Dosage Considerations – Should be Given as Follows:
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) intravenously (IV) every 8 weeks for a total of 4 doses administered with premedication and concomitant medications

Premedication and concomitant medications

• Somatostatin analogs
  • Before initiating lutetium Lu 177-dota-tate: Discontinue long-acting somatostatin analogs (e.g., long-acting octreotide) for at least 4 weeks beforehand; administer short-acting octreotide as needed; discontinue at least 24 hours before initiating lutetium Lu 177-dota-tate
  • During treatment: Administer long-acting octreotide 30 mg IM between 4-24 hours after each lutetium Lu 177-dota-tate dose; do not administer long-acting octreotide within 4 weeks of each subsequent lutetium Lu 177-dota-tate dose; short-acting octreotide may be given for symptomatic management, but must be withheld for at least 24 hours before each lutetium Lu 177-dota-tate dose
  • Following lutetium Lu 177-dota-tate treatment: Continue long-acting octreotide 30 mg IM every 4 weeks after completing lutetium Lu 177-dota-tate until disease progression or for up to 18 months following treatment initiation

• Antiemetic
  • Administer antiemetics 30 min before a recommended amino acid solution

• Amino acid solution
  • Initiate IV amino acid solution 30 min before administering lutetium Lu 177-dota-tate
  • IV amino acid solution contains: L-lysine (18-24 g) and L-arginine (18-24 g) per 1.5-2.2 L; osmolarity less than 1060 mOsmol
  • Use a 3-way valve to administer amino acids using the same venous access as lutetium Lu 177-dota-tate or administer amino acids through separate venous access in the patient's other arm
  • Continue the infusion during, and for at least 3 hours after, lutetium Lu 177-dota-tate infusion
  • Do not decrease amino acid solution dose if the dose of lutetium Lu 177-dota-tate is reduced

Dosage Modifications
Renal impairment

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

Hepatic impairment

• Mild-to-moderate: No dose adjustment required
• Severe (TB greater than 3 times ULN and any AST): Not studied

Thrombocytopenia

• Grade 2, 3, or 4
  • Withhold dose until complete or partial resolution (grade 0 to 1), then resume dose at 3.7 GBq (100 mCi) with complete or partial resolution
  • If reduced dose does not result in grade 2, 3, or 4 thrombocytopenia, administer at 7.4 GBq (200 mCi) for the next dose
  • Permanently discontinue for grade 2 or greater thrombocytopenia requiring a treatment delay 16 weeks or more

• Grade 2, 3, or 4 recurrence
  • Permanently discontinue

Anemia and neutropenia

• Grade 3 or 4
  • Withhold dose until complete or partial resolution (grade 0, 1, or 2), then resume dose at 3.7 GBq (100 mCi) with complete or partial resolution
  • If reduced dose does not result in grade 3 or 4 anemia or neutropenia, administer at 7.4 GBq (200 mCi) for the next dose
  • Permanently discontinue for grade 3 or greater thrombocytopenia requiring a treatment delay of 6 weeks or more

• Grade 3 or 4 recurrence
  • Permanently discontinue

Renal toxicity

• Renal toxicity definition
  • CrCl less than 40 mL/min OR
  • CrCl decreased 40% from baseline OR
  • Baseline serum creatinine increased 40%

• Actions
  • Withhold dose until complete resolution
  • Resume dose at 3.7 GBq (100 mCi) in patients with complete resolution
  • If reduced dose does not result in renal toxicity, administer at 7.4 GBq (200 mCi) for the next dose
  • Permanently discontinue for renal toxicity requiring a treatment delay 16 weeks or more

Hepatotoxicity

• Hepatotoxicity definition
  • Bilirubinemia greater than 3 times ULN (Grade 3 or 4) OR
  • Hypoalbuminemia less than 30 g/L with a decreased prothrombin ratio of less than 70%

• Actions
  • Withhold dose until complete resolution
  • Resume dose at 3.7 GBq (100 mCi) in patients with complete resolution
  • If reduced dose does not result in hepatotoxicity, administer at 7.4 GBq (200 mCi) for the next dose
  • Permanently discontinue for hepatotoxicity requiring a treatment delay 16weeks or more

Other nonhematologic toxicity

• Grade 3 or 4
  • Withhold dose until complete or partial resolution (grade 0-2), then resume dose at 3.7 GBq (100 mCi) with complete or partial resolution
  • If reduced dose does not result in grade 3 or 4 toxicity, administer at 7.4 GBq (200 mCi) for the next dose
  • Permanently discontinue for grade 3 or greater toxicity requiring a treatment delay of 16 weeks or more

• Grade 3 or 4 recurrence
  • Permanently discontinue

Dosing Considerations

• Verify pregnancy status of females of reproductive potential before initiating
• Safety and efficacy not established in pediatric patients

Common side effects of lutetium Lu 177-dota-tate include:

• Low lymphocytes (lymphopenia)
• Creatinine increased
• High blood sugar (hyperglycemia)
• Anemia
• Increased GGT
• Increased alkaline phosphatase
• Nausea
• Low white blood cells (leukopenia)
• Vomiting
• Low platelets (thrombocytopenia)
• AST increased
• ALT increased
• Fatigue
• High uric acid levels in the blood (hyperuricemia)
• Low blood calcium (hypocalcemia)
• Blood bilirubin increased
• Low blood potassium (hypokalemia)
• Abdominal pain
• Diarrhea
• Low white blood cells (neutropenia)
• Decreased appetite
• High blood potassium (hyperkalemia)
• High blood sodium (hypernatremia)
• Headache
• Dizziness
• Swelling of extremities
• Low blood sugar (hypoglycemia)
• Flushing
• Back pain
• Anxiety
• Renal failure
• Hair loss 
• High blood pressure (hypertension)
• Pain in extremities
• Cough
• Constipation
• Fever
• Changes in taste
• Radiation-related toxicity to urinary
• Atrial fibrillation
• Muscle pain
• Neck pain

This document does not contain all possible side effects and others may occur. Check with your physician for additional information about side effects.

If your doctor has directed you to use this medication, your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them. Do not start, stop, or change the dosage of any medicine before checking with your doctor, health care provider or pharmacist first.

Lutetium Lu 177- dota-tate has no listed severe interactions with other drugs.
Lutetium Lu 177- dota-tate has no listed serious interactions with other drugs.
 

Moderate interactions of lutetium Lu 177-dota-tate include:

• lanreotide
• octreotide
• pasireotide
• siponimod

Lutetium Lu 177- dota-tate has no listed mild interactions with other drugs.
 

This document does not contain all possible interactions. Therefore, before using this product, tell your doctor or pharmacist of all the products you use. Keep a list of all your medications with you, and share the list with your doctor and pharmacist. Check with your physician if you have health questions or concerns.

Warnings
 

This medication contains lutetium Lu 177-dota-tate. Do not take Lutathera if you are allergic to lutetium Lu 177-dota-tate or any ingredients contained in this drug.

Keep out of reach of children. In case of overdose, get medical help or contact a Poison Control Center immediately.

Contraindications

• None

Effects of Drug Abuse

• No information available

Short-Term Effects

• See "What Are Side Effects Associated with Using Lutetium Lu 177-Dota-Tate?”

Long-Term Effects

• See "What Are Side Effects Associated with Using Lutetium Lu 177-Dota-Tate?”

Cautions

• The 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
• Neuroendocrine hormonal crises, manifesting with flushing, diarrhea, bronchospasm, and hypotension, reported; typically occurs during or within 24 hr after initial dose; monitor patients for flushing, diarrhea, hypotension, bronchoconstriction, or other signs and symptoms of tumor-related hormonal release; administer IV somatostatin analogs, fluids, corticosteroids, and electrolytes as indicated
• Can cause fetal harm and infertility in males and females based on mechanism of action

Drug interaction overview

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

Pregnancy and Lactation

Based on its mechanism of action, lutetium Lu 177-dota-tate can cause fetal harm and infertility. No data are available regarding lutetium Lu 177-dota-tate use in pregnant women; however, all radiopharmaceuticals have the potential to cause fetal harm. Pregnant women should be advised of the risk to a fetus. The pregnancy status of females of reproductive potential should be verified before initiating lutetium Lu 177-dota-tate.

Females of reproductive potential are advised to use effective contraception during treatment with lutetium Lu 177-dota-tate and for 7 months after the final dose. Males with female partners of reproductive potential are advised to use effective contraception during and for 4 months after the final dose of lutetium Lu 177-dota-tate.

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. Because of the potential risk for serious adverse reactions in breastfed infants, breastfeeding is not recommended during treatment with lutetium Lu 177-dota-tate and for 2.5 months after the final dose.