Note: Premedications and concomitant medications are required.
Gastroenteropancreatic neuroendocrine tumors: IV: 7.4 GBq (200 mCi) every 8 weeks for a total of 4 doses (Strosberg 2017).
Premedication and concomitant medications:
Somatostatin analogs: Discontinue long-acting somatostatin analogs (eg, long-acting octreotide) at least 4 weeks prior to initiating lutetium Lu 177 dotatate therapy. Administer short-acting octreotide in the interim as needed, but discontinue at least 24 hours prior to initiating lutetium Lu 177 dotatate therapy. During lutetium Lu 177 dotatate therapy, administer long-acting octreotide 30 mg IM between 4 to 24 hours after each lutetium Lu 177 dotatate dose. Do not administer long-acting octreotide within 4 weeks of each subsequent lutetium Lu 177 dotatate dose; short-acting octreotide may be given for symptomatic management, but discontinue at least 24 hours before each lutetium Lu 177 dotatate dose. Continue long-acting octreotide 30 mg IM every 4 weeks after completion of the full course of lutetium Lu 177 dotatate treatment until disease progression or for up to 18 months following treatment initiation.
Antiemetic: Administer antiemetics before the recommended amino acid solution.
Amino acid solution: Initiate an IV amino acid solution 30 minutes before administering lutetium Lu 177 dotatate. The solution should contain L-lysine (between 18 to 25 g) and L-arginine (between 18 to 25 g) in a total volume of 1 to 2 L and have an osmolarity of <1,050 mOsmol/L. Continue the infusion during and for at least 3 hours after the lutetium Lu 177 dotatate dose; do not decrease the dose of the amino acid solution if the dose of lutetium Lu 177 dotatate is reduced. See "Administration".
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Note: Calculate CrCl using the Cockcroft-Gault equation with actual body weight.
Renal impairment prior to treatment initiation:
CrCl ≥30 mL/minute: No dosage adjustment necessary. Monitor renal function more frequently; patients may be at a greater risk of toxicity.
CrCl <30 mL/minute: There are no dosage adjustments provided in the manufacturer's labeling (has not been studied).
End-stage renal disease: There are no dosage adjustments provided in the manufacturer's labeling (has not been studied).
Renal toxicity during treatment:
CrCl <40 mL/minute, or 40% increase in baseline serum creatinine, or 40% decrease in baseline CrCl: Withhold lutetium Lu 177 dotatate dose until complete resolution or return to baseline; resume therapy at a reduced dose of 3.7 GBq (100 mCi) in patients with complete resolution. If the reduced dose does not result in renal toxicity, administer lutetium Lu 177 dotatate at 7.4 GBq (200 mCi) for the next dose. Permanently discontinue lutetium Lu 177 dotatate for renal toxicity requiring a treatment delay of ≥16 weeks, or for recurrent renal toxicity.
Hepatic impairment prior to treatment initiation:
Mild or moderate impairment: No dosage adjustment is necessary.
Severe impairment (bilirubin >3 times ULN and any AST): There are no dosage adjustments provided in the manufacturer's labeling (has not been studied).
Hepatotoxicity during treatment:
Bilirubin >3 times ULN (grade 3 or 4) or albumin <30 g/L with a prothrombin ratio <70%: Withhold lutetium Lu 177 dotatate dose until complete resolution or return to baseline; resume therapy at a reduced dose of 3.7 GBq (100 mCi) in patients with complete resolution or return to baseline. If the reduced dose does not result in hepatotoxicity, administer lutetium Lu 177 dotatate at 7.4 GBq (200 mCi) for the next dose. Permanently discontinue lutetium Lu 177 dotatate for hepatotoxicity requiring a treatment delay of ≥16 weeks, or for recurrent hepatotoxicity.
Refer to adult dosing.
Hematologic toxicity
Anemia or neutropenia (grade 3 or 4): Withhold lutetium Lu 177 dotatate dose until ≤ grade 2; resume therapy at a reduced dose of 3.7 GBq (100 mCi) in patients with complete or partial resolution. If the reduced dose does not result in ≥ grade 3 anemia or neutropenia, administer lutetium Lu 177 dotatate at 7.4 GBq (200 mCi) for the next dose. Permanently discontinue lutetium Lu 177 dotatate for ≥ grade 3 anemia or neutropenia requiring a treatment delay of ≥16 weeks, or for recurrent grade 3 or 4 anemia or neutropenia.
Thrombocytopenia (grade 2, 3, or 4): Withhold lutetium Lu 177 dotatate dose until ≤ grade 1; resume therapy at a reduced dose of 3.7 GBq (100 mCi) in patients with complete or partial resolution. If the reduced dose does not result in ≥ grade 2 thrombocytopenia, administer lutetium Lu 177 dotatate at 7.4 GBq (200 mCi) for the next dose. Permanently discontinue lutetium Lu 177 dotatate for ≥ grade 2 thrombocytopenia requiring a treatment delay of ≥16 weeks, or for recurrent grade 2, 3, or 4 thrombocytopenia.
Nonhematologic toxicity:
Grade 3 or 4 toxicity: Withhold lutetium Lu 177 dotatate dose until ≤ grade 2; resume therapy at a reduced dose of 3.7 GBq (100 mCi) in patients with complete or partial resolution. If the reduced dose does not result in ≥ grade 3 toxicity, administer lutetium Lu 177 dotatate at 7.4 GBq (200 mCi) for the next dose. Permanently discontinue lutetium Lu 177 dotatate for ≥ grade 3 toxicity requiring a treatment delay of ≥16 weeks, or for recurrent grade 3 or 4 toxicity.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution, Intravenous [preservative free]:
Lutathera: 370 MBq/mL (10 mCi/mL) (1 ea)
No
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution, Intravenous:
Lutathera: 370 MBq/mL (10 mCi/mL) (1 ea)
IV: Administer as an IV infusion; do not administer as an IV bolus. Administer via the gravity or infusion pump method when administering recommended dosage; for reduced dosages following an adverse reaction, administer by infusion pump method only (using gravity method may result in incorrect volume). Refer to product labeling for further details.
Gravity method:
Insert a 2.5 cm, 20-gauge needle (short needle) into the lutetium Lu 177 dotatate vial and connect via a catheter to a 500 mL sterile NS solution. Do not allow the short needle to touch the lutetium Lu 177 dotatate solution in the vial and do not connect this short needle to the patient. Do not allow NS to flow into the lutetium Lu 177 dotatate vial prior to infusion initiation and do not inject lutetium Lu 177 dotatate directly into the NS solution.
Insert a separate 9 cm, 18-gauge (long needle) into the lutetium Lu 177 dotatate vial; ensure that this long needle touches and is secured to the bottom of the lutetium Lu 177 dotatate vial during the entire infusion. Connect the long needle to the patient by an IV catheter that is prefilled with sterile NS solution and that is used only for the lutetium Lu 177 dotatate infusion into the patient.
Use a clamp or pump to regulate the flow of the NS solution via the short needle into the lutetium Lu 177 dotatate vial at a rate of 50 to 100 mL/hour for 5 to 10 minutes, and then 200 to 300 mL/hour for an additional 25 to 30 minutes. The NS solution (entering the vial through the short needle) will carry the lutetium Lu 177 dotatate from the vial to the patient through the catheter connected to the long needle (over a total duration of 30 to 40 minutes).
During the infusion, ensure that the level of solution in the lutetium Lu 177 dotatate vial remains constant. Once the level of radioactivity is stable for at least 5 minutes, disconnect the vial from the long needle line and clamp the saline line. Once the infusion is complete, flush the line with 25 mL NS.
Infusion pump method:
Insert a 2.5 cm, 20-gauge needle (short venting needle) into the lutetium Lu 177 dotatate vial. Do not allow the short needle to touch the lutetium Lu 177 dotatate solution in the vial and do not connect this short needle directly to the patient or infusion pump.
Insert a separate 9 cm, 18-gauge (long needle) into the lutetium Lu 177 dotatate vial; ensure that this long needle touches and is secured to the bottom of the lutetium Lu 177 dotatate vial during the entire infusion.
Connect the long needle and sterile NS solution to a 3-way stopcock valve via appropriate tubing. Connect the output of the 3-way stopcock valve to tubing installed on the input side of the peristaltic infusion pump according to manufacturer's instruction.
Purge the line by opening the 3-way stopcock valve and pumping the lutetium Lu 177 dotatate infusion through the tubing until it reaches the exit of the valve. Purge the IV catheter which will be connected to the patient by opening the 3-way stopcock valve to the sterile NS solution and pumping the sterile NS solution until it exits the end of the catheter tubing.
Connect the purged IV catheter to the patient and set the 3-way stopcock valve so that the lutetium Lu 177 dotatate infusion is in line with the infusion pump. Infuse one-half the volume listed on the lutetium Lu 177 dotatate vial over a 30-minute period (~25 mL/hour). When the correct volume of lutetium Lu 177 dotatate infusion has been delivered, stop the infusion pump and then change the position of the 3-way stopcock valve so that the infusion pump is in line with the sterile NS solution. Restart the infusion pump and infuse an IV flush of 25 mL NS solution through the IV catheter to the patient.
Antiemetics: Administer antiemetics prior to amino acid solution.
Amino acid solution: Use a 3-way valve to administer the amino acid solution using the same venous access as the lutetium Lu 177 dotatate infusion, or administer the amino acid solution through a separate venous access in the patient's other arm. Continue the amino acid infusion during and for at least 3 hours after the lutetium Lu 177 dotatate infusion.
Gastroenteropancreatic neuroendocrine tumors: Treatment of somatostatin receptor-positive gastroenteropancreatic neuroendocrine tumors (GEP-NETs) in adults, including foregut, midgut, and hindgut neuroendocrine tumors.
Lutathera may be confused with Lutera
Radiopharmaceutical: Use appropriate precaution for handling, disposal, and minimizing exposure to patients and health care personnel. Use under supervision of experienced personnel. Use waterproof gloves and effective radiation shielding when handling.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Adverse drug reactions are from combination therapy trials with octreotide.
>10%:
Cardiovascular: Flushing (14%), hypertension (12%), peripheral edema (16%)
Dermatologic: Alopecia (12%)
Endocrine & metabolic: Hyperglycemia (82%), hyperkalemia (19%), hypernatremia (17%), hyperuricemia (34%), hypocalcemia (32%), hypoglycemia (15%), hypokalemia (26%), increased gamma-glutamyl transferase (66%)
Gastrointestinal: Abdominal pain (26%), decreased appetite (21%), diarrhea (26%), nausea (65%), vomiting (53%)
Hematologic & oncologic: Anemia (81%), leukopenia (55%; grades 3/4: 2%), lymphocytopenia (90%; grades 3/4: 44%), neutropenia (26%; grades 3/4: 3%), thrombocytopenia (53%; grades 3/4: 1%)
Hepatic: Increased serum alanine aminotransferase (43%), increased serum alkaline phosphatase (65%), increased serum aspartate aminotransferase (50%), increased serum bilirubin (30%)
Nervous system: Anxiety (12%), dizziness (17%), fatigue (38%), headache (17%)
Neuromuscular & skeletal: Back pain (13%), limb pain (11%)
Renal: Increased serum creatinine (85%), renal failure (13%)
Respiratory: Cough (11%)
1% to 10%:
Cardiovascular: Atrial fibrillation (5%)
Gastrointestinal: Constipation (10%), dysgeusia (8%)
Genitourinary: Urotoxicity (8%, radiation-related)
Hematologic & oncologic: Myelodysplastic syndrome (3%)
Neuromuscular & skeletal: Myalgia (5%), neck pain (5%)
Miscellaneous: Fever (8%)
There are no contraindications listed in the US manufacturer's labeling.
Canadian labeling: Additional contraindications (not in US labeling): Hypersensitivity to lutetium Lu 177 dotatate or any component of the formulation; severe renal impairment (CrCl <30 mL/minute); pregnancy.
Concerns related to adverse effects:
• Bone marrow suppression: Myelosuppression (anemia, thrombocytopenia, and neutropenia [all grades]) occurred more frequently in patients receiving lutetium Lu 177 dotatate versus long-acting octreotide. In a clinical study, the platelet nadir occurred at a median of 5.1 weeks following the first lutetium Lu 177 dotatate dose. Over two-thirds of patients who developed thrombocytopenia recovered to baseline or normal platelet levels with a median platelet recovery time of 2 months. Monitor blood counts; may require therapy interruption, dosage reduction, or permanent discontinuation.
• Gastrointestinal toxicity: Nausea, vomiting, diarrhea and abdominal pain (mostly grade 1 or 2) may commonly occur. Antiemetics are recommended prior to administration.
• Hepatotoxicity: Hepatic effects have occurred with lutetium Lu 177 dotatate administration; hepatic tumor hemorrhage, edema, or necrosis, and intrahepatic congestion and cholestasis have been reported very rarely. Patients with hepatic metastasis may have an increased risk of hepatotoxicity due to radiation exposure from lutetium Lu 177 dotatate infusion. Monitor liver transaminases, bilirubin, and albumin during treatment. May require therapy interruption, dosage reduction, or permanent discontinuation.
• Neuroendocrine hormonal crisis: Neuroendocrine hormonal crises (eg, flushing, diarrhea, bronchospasm, hypotension) have occurred (rarely) following the lutetium Lu 177 dotatate dose. Reactions typically occurred during or within 24 hours after the initial dose. Hypercalcemia was reported in a small number of patients. Monitor patients for flushing, diarrhea, hypotension, bronchoconstriction, or other signs/symptoms of tumor-related hormonal release. If necessary, administer somatostatin analogs, fluids, corticosteroids, and/or electrolytes.
• Renal toxicity: Renal failure has occurred following lutetium Lu 177 dotatate administration; the time to renal failure ranged from 3 to 36 months following infusion in one clinical trial. Some patients had underlying renal impairment or other risk factors for renal failure such as diabetes or hypertension. Administer concomitantly with a recommended amino acid solution before, during, and after lutetium Lu 177 dotatate infusion to decrease proximal tubule reabsorption (and decrease radiation exposure to the kidneys); do not decrease the dose of the amino acid solution if lutetium Lu 177 dotatate is dose reduced. Patients should urinate frequently during and after lutetium Lu 177 dotatate infusion. Monitor serum creatinine and creatinine clearance, particularly in patients with baseline renal impairment. May require therapy interruption, dosage reduction, or permanent discontinuation.
• Secondary malignancies: In clinical trials, myelodysplastic syndrome (MDS) and leukemia have been reported in a small percentage of patients who received lutetium Lu 177 dotatate. In one study, the median time to development was 28 months (range: 9 to 41 months) and 55 months (range: 32 to 155 months) for MDS and leukemia, respectively. Long-term cumulative radiation exposure is associated with an increased risk for cancer.
Disease-related concerns:
• Renal impairment: Patients with baseline mild or moderate renal impairment may be at increased risk for renal toxicity following lutetium Lu 177 dotatate administration; monitor renal function (eg, serum creatinine and calculated creatinine clearance) more frequently in patients with preexisting renal impairment. Lutetium Lu 177 dotatate has not been studied in patients with severe renal impairment.
Special handling:
• Radiopharmaceutical: Use appropriate precautions for handling, disposal, and minimizing exposure to patients, health care personnel, and household contacts. Use only under supervision of individuals with experience/training in the handling of radioactive materials approved by the applicable regulatory authority. Radiation may be detected in the urine for up to 30 days following lutetium Lu 177 dotatate infusion; administration of this agent contributes to the patient's long-term radiation exposure which is associated with an increased cancer risk.
None known.
5-Aminosalicylic Acid Derivatives: May enhance the myelosuppressive effect of Myelosuppressive Agents. Risk C: Monitor therapy
BCG (Intravesical): Myelosuppressive Agents may diminish the therapeutic effect of BCG (Intravesical). Risk X: Avoid combination
Chloramphenicol (Ophthalmic): May enhance the adverse/toxic effect of Myelosuppressive Agents. Risk C: Monitor therapy
Cladribine: May enhance the myelosuppressive effect of Myelosuppressive Agents. Risk X: Avoid combination
CloZAPine: Myelosuppressive Agents may enhance the adverse/toxic effect of CloZAPine. Specifically, the risk for neutropenia may be increased. Risk C: Monitor therapy
Corticosteroids (Systemic): May diminish the therapeutic effect of Lutetium Lu 177 Dotatate. Management: Avoid repeated use of high-doses of corticosteroids during treatment with lutetium Lu 177 dotatate. Use of corticosteroids is still permitted for the treatment of neuroendocrine hormonal crisis. The effects of lower corticosteroid doses is unknown. Risk D: Consider therapy modification
Deferiprone: Myelosuppressive Agents may enhance the neutropenic effect of Deferiprone. Management: Avoid the concomitant use of deferiprone and myelosuppressive agents whenever possible. If this combination cannot be avoided, monitor the absolute neutrophil count more closely. Risk D: Consider therapy modification
Dipyrone: May enhance the adverse/toxic effect of Myelosuppressive Agents. Specifically, the risk for agranulocytosis and pancytopenia may be increased Risk X: Avoid combination
Fexinidazole: Myelosuppressive Agents may enhance the myelosuppressive effect of Fexinidazole. Risk X: Avoid combination
Promazine: May enhance the myelosuppressive effect of Myelosuppressive Agents. Risk C: Monitor therapy
Ropeginterferon Alfa-2b: Myelosuppressive Agents may enhance the myelosuppressive effect of Ropeginterferon Alfa-2b. Management: Avoid coadministration of ropeginterferon alfa-2b and other myelosuppressive agents. If this combination cannot be avoided, monitor patients for excessive myelosuppressive effects. Risk D: Consider therapy modification
Somatostatin Analogs: May diminish the therapeutic effect of Lutetium Lu 177 Dotatate. Specifically, the therapeutic effect of Lutetium Lu 177 Dotatate may be diminished if the timing of Somatostatin Analog administration is not carried out as recommended. Management: Discontinue long-acting somatostatin analogs at least 4 weeks and short-acting octreotide at least 24 hours prior to lutetium Lu 177 dotatate dose. Administer short and long-acting octreotide during treatment as recommended. See full interaction monograph Risk D: Consider therapy modification
Evaluate pregnancy status prior to initiating therapy. Females of reproductive potential should use effective contraception during therapy and for 7 months after the final dose. Males with female partners of reproductive potential should use effective contraception during therapy and for 4 months after the final dose.
Radiation associated with lutetium Lu 177 dotatate therapy may cause infertility in males and females, which may be temporary or permanent.
Based on the mechanism of action, lutetium Lu 177 dotatate may cause fetal harm if exposure occurs during pregnancy.
It is not known if lutetium Lu 177 dotatate is present in breast milk. Due to the potential for serious adverse events in the breastfed infant, the manufacturer does not recommend breastfeeding during therapy or for 2.5 months after the final dose.
Monitor blood cell counts; serum creatinine and creatinine clearance; transaminases, bilirubin, and albumin; verify pregnancy status in females of reproductive potential prior to initiating therapy; monitor for signs/symptoms of neuroendocrine hormonal crisis (eg, flushing, diarrhea, bronchospasm, hypotension) and secondary malignancies (myelodysplastic syndrome and leukemia)
Lutetium Lu 177 dotatate is a beta- and gamma-emitting radionuclide which binds to somatostatin receptors (Strosberg 2017). It binds with highest affinity to subtype 2 receptors (SSRT2); after binding to somatostatin-expressing cells, the lutetium Lu 177 dotatate compound is internalized. Beta emission induces cellular damage by forming free radicals in somatostatin receptor-positive and surrounding cells.
Distribution: 460 L; lutetium Lu 177 dotatate distributes into kidneys, tumor lesions, liver, spleen, and (in some patients) pituitary gland and thyroid within 4 hours after administration. The maximum penetration into tissue is 2.2 mm (mean penetration: 0.67 mm).
Protein binding: Non-radioactive form of lutetium dotatate: 43% to plasma proteins
Half-life elimination: Mean terminal blood half-life: 71 ± 28 hours
Excretion: Primarily renal; prolonged elimination in the urine is expected; however, >99% of lutetium Lu 177 dotatate will be eliminated within 14 days after administration
Solution (Lutathera Intravenous)
370 mbq/ml (per each): $63,912.00
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