lutetium lu 177 dotatate

General

Genetic Implications: Genetic Implications

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


Trade Name(s)

  • Lutathera

Ther. Class.
antineoplastics

Pharm. Class.
radiopharmaceuticals

Indications

Genetic implication Somatostatin receptor-positive gastroenteropancreatic neuroendocrine tumors (GEP-NETs), including foregut, midgut, and hindgut neuroendocrine tumors.

Action

Acts as a beta-emitting radionuclide which 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 (blood concentrations)

ROUTEONSETPEAKDURATION
IVrapidend of infusionUp to 30 days

Contraindication/Precautions

Contraindicated in:

  • OB:   Pregnancy (may cause fetal harm)
  • 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:   Safety and effectiveness not established in children.

Adverse Reactions/Side Effects

CNS: anxiety, dizziness, headache, dysgeusia

CV: hypertension, peripheral edema, atrial fibrillation

Derm: alopecia, flushing

Endo: hyperglycemia, hyperuricemia, hypoglycemia, neuroendocrine hormonal crisis

F and E: hyperkalemia, hypernatremia, hypocalcemia, hypokalemia

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

GU: renal failure, ↓ fertility

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

Metabolic: ↓ appetite

MS: pain

Resp: cough

Misc: fatigue, 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): 7.4 GBq (200 mCi) every 8 wk for a total of 4 doses.

Availability

Solution for injection: 10 mCi/mL

Assessment

  • 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 to 1). Resume  Lutathera  at 3.7 GBq (100 mCi) in patients with complete or partial resolution. If reduced dose does not result in Grade 2, 3 or 4 thrombocytopenia, administer  Lutathera  at 7.4 GBq (200 mCi) for next dose. Discontinue  Lutathera  permanently for ≥Grade 2 thrombocytopenia requiring treatment delay ≥16 wk.  If Grade 2, 3, or 4 recurs,  discontinue therapy permanently.
  • If Grade 3 or 4 anemia or neutropenia occurs,  hold dose until complete or partial resolution (Grade 0, 1, or 2). Resume  Lutathera  at 3.7 GBq (100 mCi) in patients with complete or partial resolution. If reduced dose does not result in Grade 3 or 4 anemia or neutropenia, administer  Lutathera  at 7.4 GBq (200 mCi) for next dose. Permanently discontinue  Lutathera  for ≥Grade 3 anemia or neutropenia requiring treatment delay ≥16 wk.  If Grade 3 or 4 recurs,  discontinue therapy 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  Lutathera  at 3.7 GBq (100 mCi) in patients with complete resolution. If reduced dose does not result in renal toxicity, administer  Lutathera  at 7.4 GBq (200 mCi) for next dose. Permanently discontinue  Lutathera  for renal toxicity requiring treatment delay ≥16 wk.  If renal toxicity recurs,  discontinue  Lutathera  permanently.
  • Monitor AST, ALT, bilirubin and serum albumin during therapy.  If hepatotoxicity (bilirubinemia >3 × ULN (Grade 3 or 4), or hypoalbuminemia <30 g/L with ↓ prothrombin ratio <70%) occurs, hold dose until complete resolution or return to baseline. Resume  Lutathera  at 3.7 GBq (100 mCi) in patients with complete resolution or return to baseline. If reduced  Lutathera  dose does not result in hepatotoxicity, administer  Lutathera  at 7.4 GBq (200 mCi) for next dose. Permanently discontinue  Lutathera  for hepatotoxicity requiring treatment delay ≥16 wk.  If hepatotoxicity recurs,  permanently discontinue  Lutathera.

Implementation

  • Radiopharmaceutical; handle with appropriate safety measures to minimize radiation exposure. Use waterproof gloves and effective radiation shielding when handling drug. Used by or under control of health care professionals qualified by specific training and experience in safe use and handling of radiopharmaceuticals, and whose experience and training have been approved by appropriate governmental agency authorized to license use of radiopharmaceuticals. Minimize radiation exposure to patients, medical personnel, and household contacts during and after therapy consistent with institutional good 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) least 4 wk before starting therapy. Administer short-acting octreotide as needed; discontinue at least 24 hr before starting therapy.
  • Administer long-acting octreotide 30 mg IM 4 to 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 at least 24 hr before each dose.
  • Continue long-acting octreotide 30 mg IM every 4 wk after therapy is completed until disease progression or for up to 18 mos following after starting therapy.
  • Administer antiemetics before amino acid solution.

IV Administration

  • Start IV amino acid solution of L-lysine (18–25 g) and L-arginine (18–25 g) in 1–2 L volume 30 min before administering  Lutathera. Use a 3-way valve to administer amino acids using same venous access as  Lutathera  or administer amino acids through separate venous access in patient's other arm. Continue infusion during and for at least 3 hr after  Lutathera  infusion. Do not decrease dose of amino acid solution if dose of  Lutathera  is reduced to decrease reabsorption of  Lutathera  through proximal tubules and decrease radiation dose to kidneys.
  • Use aseptic technique and radiation shielding when administering  Lutathera. Use tongs when handling vial to minimize radiation exposure. Do not inject  Lutathera  directly into any other intravenous solution. Confirm amount of radioactivity of  Lutathera  in radiopharmaceutical vial with an appropriate dose calibrator before and after  Lutathera  administration. Solution is colorless to slightly yellow; do not administer solutions that are cloudy, discolored, or contain particulate matter. Dispose of any unused medicinal product or waste material in accordance with local and federal laws.
  • Intermittent Infusion:  Insert a 2.5 cm, 20 gauge needle (short needle) into  Lutathera  vial and connect via a catheter to 500 mL 0.9% NaCl (to transport  Lutathera  during infusion). Ensure short needle does not touch  Lutathera  solution in vial and do not connect this short needle directly to patient. Do not allow 0.9% NaCl to flow into  Lutathera  vial before infusion and do not inject  Lutathera  directly into 0.9% NaCl. Insert a second, 9 cm, 18 gauge needle (long needle) into  Lutathera  vial ensuring that this long needle touches and is secured to bottom of  Lutathera  vial during entire infusion. Connect long needle to patient by an IV catheter that is prefilled with 0.9% NaCl and is used exclusively for  Lutathera  infusion.
  • Rate: Use a clamp or pump to regulate flow of 0.9% NaCl via short needle into  Lutathera  vial at a rate of 50–100 mL/hr for 5 to 10 min, then 200–300 mL/hr for additional 25 to 30 min (0.9% NaCl entering vial through short needle will carry  Lutathera  from vial to patient via catheter connected to long needle over a total duration of 30 to 40 min). During infusion, ensure level of solution in  Lutathera  vial remains constant. Disconnect vial from long needle line and clamp 0.9% NaCl once level of radioactivity is stable for at least 5 min. Follow infusion with an IV flush of 25 mL 0.9% NaCl.
  • Intermittent Infusion:  Use when administering reduced dose of  Lutathera after decreasing dose for an adverse reaction; gravity method may result in delivery of incorrect volume, if dose is not adjusted before administration. Insert 2.5 cm, 20 gauge needle (short venting needle) into  Lutathera vial. Ensure short needle does not touch  Lutathera  solution in vial and do not connect short needle directly to patient or infusion pump. Insert second, 9 cm, 18 gauge needle (long needle) into  Lutathera  vial ensuring long needle touches and is secured to bottom of  Lutathera  vial during entire infusion. Connect long needle and 0.9% NaCl to 3­way stopcock valve via appropriate tubing. Connect output of 3-way stopcock valve to tubing installed on input side of peristaltic infusion pump according to manufacturer's instruction. Purge line by opening 3-way stopcock valve and pumping  Lutathera  solution through tubing until it reaches exit of valve. Purge IV catheter connected to patient by opening 3-way stopcock valve to 0.9% NaCl and pumping 0.9% NaCl until it exits end of catheter tubing. Connect purged catheter to patient and set 3-way stopcock valve so  Lutathera solution is in line with infusion pump.
  • Rate: Infuse one-half volume listed on  Lutathera  vial over a 30 min period (25 mL/hr). When correct volume of  Lutathera  delivered, stop infusion pump and change position of 3-way stopcock valve so that infusion pump is in line with 0.9% NaCl. Restart infusion pump and infuse an IV flush of 25 mL of 0.9% NaCl through catheter to patient.
  • Y-Site Incompatibility: Do not mix with or infuse with other drug or solutions.

Patient/Family Teaching

  • Inform patient that  Lutathera  contributes to overall long-term radiation exposure. Long-term cumulative radiation exposure is associated with increased risk for cancer. Radiation can be detected in urine for up to 30 days after  Lutathera  administration. Provide instructions to patient for follow-up radiation protection at home to minimize radiation exposure household contacts.
  • Advise patient to urinate frequently during and after administration of  Lutathera  to decrease radiation dose to kidneys.
  • Advise patient to notify health care professional if signs and symptoms of infection (fever, chills, dizziness, shortness of breath, increased 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 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.
  • Emphasize importance of regular lab tests to monitor for side effects.

Evaluation/Desired Outcomes

Improvement in progression-free survival.

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