LUTATHERA® (lutetium Lu 177 dotatate) Regimen and Administration Procedures

Important safety instructions1

LUTATHERA is a radiopharmaceutical; handle with appropriate safety measures to minimize radiation exposure. Use waterproof gloves and effective radiation shielding when handling LUTATHERA. Radiopharmaceuticals, including LUTATHERA, should be used by or under the control of physicians who are qualified by specific training and experience in the safe use and handling of radiopharmaceuticals, and whose experience and training have been approved by the appropriate governmental agency authorized to license the use of radiopharmaceuticals. Verify pregnancy status of females of reproductive potential prior to initiating LUTATHERA.

“ALARA” principle: keeping radiation exposure “as low as reasonably achievable”2

ALARA is the guiding principle of radiation safety. It means that even a small radiation dose should be avoided if there is no benefit to receiving it. It includes 3 basic protective measures:

TIME: minimize time near a radiation source. Spend only the time needed to complete your job near the radiation source, and then leave the area.

DISTANCE: maximize distance from a radiation source. Stay as far away as you can from the radiation source.

SHIELDING: use appropriate shielding between yourself and a radiation source. Put appropriate materials between you and the radiation source. The appropriate materials will depend on what type of radiation the source emits.

Safety procedures1,3

You should follow these procedures, in addition to your institution’s radiation safety guidelines, whenever handling or administering LUTATHERA:

  • Use disposable plastic, latex, or rubber gloves
  • Wear a lab coat, which must be monitored before leaving the laboratory
  • Wear safety glasses
  • Minimize handling time
  • Use tongs to handle unshielded sources and potentially contaminated vessels
  • Use disposable absorbent liners on trays
  • Ensure that waste and medical consumables exposed to radioactivity are disposed of in compliance with your institution’s radiation safety policies

Radiation associated with LUTATHERA

The 177Lu isotope in LUTATHERA decays with a half-life of 6.647 days1 and emits 2 types of radiation4:

  • A low-to-medium-energy β particle, which is predominantly absorbed within the body of the patient
  • γ radiation at a low quantity and low-to-medium energy

These characteristics help keep radiation exposure to bystanders, such as medical personnel and caregivers, within the established regulatory guidance.5

Preparing for LUTATHERA administration

Absorbent drapes should be used to cover vulnerable areas in the patient room and bathroom. This might include certain areas of the floor and toilet.3

Patients may arrive in street clothes but may change into hospital gowns before the LUTATHERA infusion, so that their gowns may be quarantined in the event of a radiation spill.

The patient should be provided with access to an isolated bathroom unavailable to the general public as 177Lu is excreted in the urine, which will therefore contain radioactive material. The patient should be encouraged to urinate as frequently as possible to help eliminate radioactive material concentrated in the urine. Patients should be instructed regarding procedures to avoid contamination of the bathroom. Men should sit on the toilet to urinate. Patients should double-flush the toilet after use.

In case of a radiation spill

If a radiation spill occurs, you should always follow the guidance of your institution’s radiation safety department.

Nausea and vomiting are often seen during the infusion procedure.1 Vomit from a patient who has received LUTATHERA should be considered radioactive and cleaned up following the procedures for a radiation spill. Patients should be administered an antiemetic as described in premedication and concomitant medications.

Urine and feces from a patient who has received LUTATHERA is radioactive and should be cleaned up following the procedures for a radiation spill.

The LUTATHERA regimen1

The recommended treatment regimen consists of 7.4 GBq (200 mCi) IV every 8 weeks, for a total of 4 doses. Following each dose, the patient should receive long-acting octreotide 30 mg IM between 4 and 24 hours after each LUTATHERA dose. Long-acting octreotide 30 mg IM should be continued every 4 weeks after completing LUTATHERA until disease progression or for up to 18 months following LUTATHERA treatment initiation.

Administer premedication and concomitant medications..

In case of toxicity: Interval between doses can be extended up to 16 weeks as needed. Information is provided in the LUTATHERA full prescribing information as to when treatment with LUTATHERA should be suspended, the dose adjusted, or treatment permanently discontinued due to adverse reactions, including thrombocytopenia, anemia and neutropenia, renal toxicity, hepatotoxicity, and other non-hematologic toxicity.1

Premedication and concomitant medications

Somatostatin analogs1
vector1
Discontinue long-acting somatostatin analogs (eg, long-acting octreotide) for at least 4 weeks prior to initiating LUTATHERA.
vetcor2
Short-acting octreotide may be given for acute or urgent symptomatic management during LUTATHERA treatment, but must be withheld for at least 24 hours prior to each LUTATHERA dose.
vector3
During LUTATHERA treatment, administer long-acting octreotide 30 mg intramuscularly between 4 to 24 hours after each LUTATHERA dose.
vector1
After completing the LUTATHERA 4-dose regimen, continue long-acting octreotide 30 mg intramuscularly every 4 weeks until disease progression or for up to 18 months following treatment initiation.
Antiemetics and amino acids1

An antiemetic should be administered before the start of the amino acid solution infusion to help avoid treatment-related nausea and vomiting.

An IV infusion of an amino acid solution is started 30 minutes before LUTATHERA administration and continued during and for at least 3 hours after. Always administer the full amino acid solution treatment, even if administering a reduced dose of LUTATHERA.

Infusion schedule and procedures

The following is a brief overview of the administration procedure. For the full procedure, please see LUTATHERA full prescribing information.

In the LUTATHERA infusion method, a saline solution carries the LUTATHERA dose into the IV infusion catheter. A clamp or pump is used to regulate the saline flow, and thus the rate of LUTATHERA infusion. The amino acid solution is delivered using the same venous access or separately into the patient’s other arm through a venous access.1

The LUTATHERA infusion is usually not administered by the nurse. The radiopharmaceutical infusion will usually be administered by a nuclear medicine technologist or nuclear medicine physician, depending upon the institution. These individuals are sometimes called the “authorized user.”

The LUTATHERA infusion should be conducted over the course of 30 to 40 minutes. LUTATHERA must not be administered as an intravenous bolus. Use a clamp or pump to regulate the flow of the sodium chloride solution via the short needle into the LUTATHERA vial at a rate of 50 mL/hour to 100 mL/hour for 5 to 10 minutes and then 200 mL/hour to 300 mL/hour for an additional 25 to 30 minutes.1

The LUTATHERA infusion can be disconnected once the level of radioactivity is stable for at least 5 minutes (this is the only parameter to determine the procedure’s end).1

Use radiation shielding and tongs whenever handling the LUTATHERA vial to minimize exposure.1

Downloadable resources for nursing care and about the administration of LUTATHERA are available here.

IM, intramuscular; IV, intravenous.

References: 1. LUTATHERA®[prescribing information]. Millburn, NJ: Advanced Accelerator Applications USA, Inc.; 2020. 2. Centers for Disease Control and Prevention. https://www.cdc.gov/nceh/radiation/alara.html. Accessed October 3, 2017. 3. Data on file. Advanced Accelerator Applications USA, Inc. 4. Olmstead C, Cruz K, Stodilka R, Zabel P, Wolfson R. Quantifying public radiation exposure related to lutetium-177 octreotate therapy for the development of a safe outpatient treatment protocol. Nucl Med Commun. 2015;36(2):129-134. 5. Calais PJ, Turner JH. Radiation safety of outpatient 177Lu-octreotate radiopeptide therapy of neuroendocrine tumors. Ann Nucl Med. 2014;28(6):531-539.

IMPORTANT SAFETY INFORMATION

WARNINGS AND PRECAUTIONS

  • Radiation Exposure: Treatment with LUTATHERA contributes to a patient’s overall long-term cumulative radiation exposure and is associated with an increased risk for cancer. Radiation can be detected in the urine for up to 30 days following LUTATHERA administration. Minimize radiation exposure to patients, medical personnel, and household contacts during and after treatment with LUTATHERA 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.
  • Myelosuppression: In NETTER-1 clinical trial, myelosuppression occurred more frequently in patients receiving LUTATHERA with long acting octreotide at the following rates (all grades/grade 3 or 4): anemia (81%/0), thrombocytopenia (53%/1%), and neutropenia (26%/3%). Blood cell counts must be monitored prior to, during, and after treatment. Withhold, reduce dose, or permanently discontinue based on severity of myelosuppression.
  • Secondary Myelodysplastic Syndrome and Leukemia: In NETTER-1, with a median follow-up time of 24 months, myelodysplastic syndrome (MDS) was reported in 2.7% of patients receiving LUTATHERA with long-acting octreotide. In ERASMUS, a Phase II clinical study, 16 patients (2%) developed MDS and 4 (0.5%) developed acute leukemia. The median time to the development of MDS was 28 months (9 to 41 months) and 55 months (32 to 155 months) for acute leukemia.
  • Renal Toxicity: Treatment with LUTATHERA will expose kidneys to radiation, which may impair renal function. In ERASMUS <1% of patients developed renal failure 3 to 36 months following LUTATHERA. Monitor serum creatinine and creatinine clearance to assess changes in renal function. Advise patients to urinate frequently during and after administration of LUTATHERA. A concomitant intravenous infusion of amino acids before, during, and after LUTATHERA administration is mandatory for renal protection. Patients with baseline renal impairment may be at greater risk of toxicity. Perform more frequent assessments of renal function in patients with mild or moderate impairment. Withhold, reduce dose, or permanently discontinue based on severity of renal toxicity. Do not decrease the dose of amino acid solution if the dose of LUTATHERA is reduced. LUTATHERA has not been studied in patients with severe renal impairment (CrCL < 30 mL/min).
  • Hepatotoxicity: In ERASMUS, <1% of patients were reported to have hepatic tumor hemorrhage, edema, or necrosis, with one patient experiencing intrahepatic congestion and cholestasis. Patients with hepatic metastasis may be at increased risk of hepatotoxicity due to radiation exposure. Monitor transaminases, bilirubin, and serum albumin during treatment. Withhold, reduce dose, or permanently discontinue based on severity of hepatic impairment.
  • Neuroendocrine hormonal crisis: Manifesting with flushing, diarrhea, bronchospasm and hypotension, neuroendocrine hormonal crisis occurred in <1% of patients in ERASMUS and typically occurred during or within 24 hours following the initial LUTATHERA dose. Monitor patients for flushing, diarrhea, hypotension, bronchoconstriction or other signs and symptoms of tumor-related hormonal release. Administer intravenous somatostatin analogs, fluids, corticosteroids, and electrolytes as indicated.
  • Embryo-Fetal Toxicity: LUTATHERA can cause fetal harm. Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment and for 7 months after the final dose. Advise males with female partners of reproductive potential to use effective contraception during treatment and for 4 months after the final dose. Verify pregnancy status of females of reproductive potential prior to initiating LUTATHERA.
  • Risk of Infertility: LUTATHERA may cause infertility in males and females. Radiation absorbed by testes and ovaries from the recommended cumulative LUTATHERA dose falls within the range in which temporary or permanent infertility can be expected following external beam radiotherapy.

ADVERSE REACTIONS

The most common Grade 3-4 adverse reactions (≥ 4% with a higher incidence in LUTATHERA arm) observed in NETTER-1 were lymphopenia (44%), increased GGT (20%), vomiting (7%), nausea (5%), elevated AST (5%), increased ALT (4%), hyperglycemia (4%), and hypokalemia (4%).

In ERASMUS, the following serious adverse reactions have been observed with a median follow-up time of more than 4 years after treatment with LUTATHERA: myelodysplastic syndrome (2%), acute leukemia (1%), renal failure (2%), hypotension (1%), cardiac failure (2%), myocardial infarction (1%), and neuroendocrine hormonal crisis (1%). Patients should be counseled and monitored in accordance with the LUTATHERA Prescribing Information.

DRUG INTERACTIONS

Somatostatin and its analogs competitively bind to somatostatin receptors and may interfere with the efficacy of LUTATHERA. Discontinue long-acting somatostatin analogs at least 4 weeks and short-acting octreotide at least 24 hours prior to each LUTATHERA dose. Administer short- and long-acting octreotide during LUTATHERA treatment as recommended.

Corticosteroids can induce down-regulation of subtype 2 somatostatin receptors (SSTR2). Avoid repeated administration of high doses of glucocorticosteroids during treatment with LUTATHERA.

SPECIFIC POPULATIONS

  • Lactation: Because of the potential risk for serious adverse reactions in breastfed infants, advise women not to breastfeed during treatment with LUTATHERA and for 2.5 months after the final dose.

To report SUSPECTED ADVERSE REACTIONS, contact Novartis Pharmaceuticals Corporation at 1-888-669-6682 or www.report.novartis.com/, or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

Please see full Prescribing Information.

Distributed by: Advanced Accelerator Applications USA, Inc., NJ 07041

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