General

High Alert Medication: This medication bears a heightened risk of causing significant patient harm when it is used in error.

Genetic Implications:

Pronunciation:
loo-tee-she-um loo 177 doe-tah-tate

Trade Name(s)

• Lutathera

Ther. Class.

antineoplastics

Pharm. Class.

radiopharmaceuticals

Indications

 Somatostatin receptor-positive gastroenteropancreatic neuroendocrine tumors, including foregut, midgut, and hindgut neuroendocrine tumors.

Action

Acts as a beta-emitting radionuclide that binds to somatostatin receptors, particularly subtype 2 receptors. Once bound to these receptors, the compound is internalized and then emits beta radiation, which leads to cellular damage in somatostatin receptor-positive cells and in surrounding cells.

Therapeutic Effect(s):

Improvement in progression-free survival.

Pharmacokinetics

Absorption: IV administration results in complete bioavailability.

Distribution: Extensively distributed to extravascular tissues.

Metabolism and Excretion: Does not undergo hepatic metabolism. Primarily excreted in urine.

Half-life: 71 hr.

TIME/ACTION PROFILE (plasma concentrations)

Contraindication/Precautions

Contraindicated in:

• OB:   Pregnancy;
• Lactation:  Lactation.

Use Cautiously in:

• Renal impairment;
• Severe hepatic impairment;
• Hepatic metastases (↑ risk of hepatotoxicity);
• Rep:   Women of reproductive potential and men with female partners of reproductive potential;
• Pedi:   Children <12 yr (safety and effectiveness not established).

Adverse Reactions/Side Effects

CV: hypertension, peripheral edema, atrial fibrillation

Derm: alopecia, flushing

Endo: hyperglycemia, hyperuricemia, hypoglycemia, neuroendocrine hormonal crisis

F and E: hyperkalemia, hypernatremia, hypocalcemia, hypokalemia

GI: abdominal pain, constipation, diarrhea, nausea, vomiting, HEPATOTOXICITY

GU: renal failure, ↓ fertility

Hemat: anemia, leukopenia, lymphopenia, NEUTROPENIA, thrombocytopenia, LEUKEMIA, MYELODYSPLASTIC SYNDROME

Metabolic: ↓ appetite

MS: pain

Neuro: anxiety, dizziness, fatigue, headache, dysgeusia

Resp: cough

Misc: HYPERSENSITIVITY REACTIONS (including angioedema), fever

* CAPITALS indicate life-threatening.
Underline indicate most frequent.

Interactions

Drug-Drug

• Effectiveness may be ↓ by  somatostatin analogs, including  octreotide ; discontinue long-acting somatostatin analogs ≥4 wk and short-acting somatostatin analogs ≥24 hr before each dose.
• Effectiveness may be ↓ by  corticosteroids ; avoid repeated administration of high-dose corticosteroids during treatment.

Route/Dosage

IV (Adults and Children ≥12 yr): 7.4 GBq (200 mCi) every 8 wk for a total of 4 doses.

Availability

Solution for injection: 10 mCi/mL

Assessment

• Observe patient during infusion and for ≥2 hr after infusion is completed. Assess for signs of hypersensitivity reactions (urticaria, dizziness, fever, rash, rigors, pruritus, nausea, flushing, hypotension, dyspnea, chest pain, angioedema, anaphylaxis).  If Grade 1 or 2  hypersensitivity reaction occurs, premedicate before subsequent doses.  If Grade 3 or 4 hypersensitivity reaction occurs, permanently discontinue.
• Monitor for signs and symptoms of neuroendocrine hormonal crisis (flushing, diarrhea, hypotension, bronchoconstriction, other signs and symptoms of tumor-related hormonal release) periodically during. Administer IV somatostatin analogs, fluids, corticosteroids, and electrolytes as indicated.

Lab Test Considerations:

Verify negative pregnancy test before starting therapy.

• Monitor CBC and platelet count during therapy.  If Grade 2, 3, or 4 thrombocytopenia occurs,  hold dose until complete or partial resolution (Grade 0–1). Resume at 3.7 GBq (100 mCi) in patients with complete or partial resolution. If ↓ dose does not result in Grade 2, 3, or 4 thrombocytopenia, administer at 7.4 GBq (200 mCi) for next dose. Discontinue permanently for ≥Grade 2 thrombocytopenia requiring treatment delay ≥16 wk.  If Grade 2, 3, or 4 recurs,  discontinue permanently.
• If Grade 3 or 4 anemia or neutropenia occurs,  hold dose until complete or partial resolution (Grade 0, 1, or 2). Resume at 3.7 GBq (100 mCi) in patients with complete or partial resolution. If ↓ dose does not result in Grade 3 or 4 anemia or neutropenia, administer at 7.4 GBq (200 mCi) for next dose. Permanently discontinue for ≥Grade 3 anemia or neutropenia requiring treatment delay ≥16 wk.  If Grade 3 or 4 recurs,  discontinue permanently.
• Monitor serum creatinine and calculated CCr during therapy.  If renal toxicity (CCr <40 mL/min; calculate using Cockcroft Gault with actual body weight, or 40% ↑ in baseline serum creatinine, or 40% ↓ in baseline CCr; calculate using Cockcroft Gault with actual body weight) occurs,  hold dose until complete resolution or return to baseline. Resume at 3.7 GBq (100 mCi) if complete resolution. If ↓ dose does not result in renal toxicity, administer at 7.4 GBq (200 mCi) for next dose. Permanently discontinue for renal toxicity requiring treatment delay ≥16 wk.  If renal toxicity recurs,  discontinue permanently.
• Monitor AST, ALT, bilirubin, and serum albumin during therapy.  If hepatotoxicity (bilirubin >3 times upper limit of normal [Grade 3 or 4], or albumin <3 g/dL with INR >1.5) occurs, hold dose until complete resolution or return to baseline. Resume at 3.7 GBq (100 mCi) if complete resolution or return to baseline. If ↓ dose does not result in hepatotoxicity, administer at 7.4 GBq (200 mCi) for next dose. Permanently discontinue for hepatotoxicity requiring treatment delay ≥16 wk.  If hepatotoxicity recurs,  permanently discontinue .

Implementation

• High Alert: Radiopharmaceutical; handle with appropriate safety measures to minimize radiation exposure. Use waterproof gloves and radiation shielding when handling drug. Used by or under control of health care professionals who are licensed and qualified by specific training and experience in safe use and handling and whose experience and training have been approved by appropriate governmental agency. Minimize radiation exposure to patients, medical personnel, and household contacts during and after therapy consistent with institutional radiation safety practices, patient management procedures, Nuclear Regulatory Commission patient-release guidance, and instructions to the patient for follow-up radiation protection at home.
• Discontinue long-acting somatostatin analogs (long-acting octreotide) ≥4 wk before starting therapy. Administer short-acting octreotide as needed; discontinue ≥24 hr before starting therapy.
• Administer long-acting octreotide 30 mg IM 4–24 hr after each dose during therapy. Do not administer long-acting octreotide within 4 wk of each subsequent dose. May give short-acting octreotide to manage symptoms during therapy, but hold for ≥24 hr before each dose.
• Continue long-acting octreotide 30 mg IM every 4 wk after therapy is completed until disease progression or for 18 mo following after starting therapy.
• Administer antiemetics before amino acid solution.

Patient/Family Teaching

• Explain purpose and side effects of medication to patient. Advise patient to read  Patient Information  before starting therapy. Emphasize importance of regular lab tests to monitor for side effects. Inform patient that long-term radiation exposure is associated with ↑ risk for cancer. Radiation can be detected in urine for up to 30 days after administration. Provide instructions to patient for follow-up radiation protection at home to minimize radiation exposure of household contacts.
• Advise patient to urinate frequently during and after administration to ↓ radiation dose to kidneys.
• Advise patient to notify health care professional if signs and symptoms of infection (fever, chills, dizziness, shortness of breath, ↑ bleeding or bruising) and neuroendocrine hormonal crisis occur.
• Caution patient to avoid crowds and persons with known infections. Instruct patient to use soft toothbrush and electric razor and to avoid falls. Patient should also be cautioned not to drink alcoholic beverages or to take products containing aspirin or NSAIDs; may precipitate GI hemorrhage.
• Inform patient of risk for secondary cancers, including myelodysplastic syndrome and acute leukemia.
• Rep:  May cause fetal harm. Advise females of reproductive potential to use effective contraception during for 7 mo after last dose and to avoid breastfeeding during therapy and for 2.5 mo after last dose. Advise males with female partners of reproductive potential to use effective contraception during and for 4 mo after last dose. May impair male and female fertility.

Evaluation/Desired Outcomes

Improvement in progression-free survival.