lutetium Lu 177-dota-tate (Rx)

Brand and Other Names:Lutathera
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Dosing & Uses

AdultPediatric

Dosage Forms & 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

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) IV q8weeks 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 (eg, long-acting octreotide) for at least 4 weeks beforehand; administer short-acting octreotide as needed; discontinue at least 24 hr before initiating lutetium Lu 177-dota-tate
    • During treatment: Administer long-acting octreotide 30 mg IM between 4-24 hr 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 hr before each lutetium Lu 177-dota-tate dose
    • Following lutetium Lu 177-dota-tate treatment: Continue long-acting octreotide 30 mg IM q4weeks 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 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 <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 a separate venous access in the patient’s other arm
    • Continue the infusion during, and for at least 3 hr 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/min): No dose adjustment required; however, patients may be at greater risk of toxicity; perform more frequent assessments of renal function
  • Severe (CrCl <30 mL/min) or end-stage renal disease: Not studied

Hepatic impairment

  • Mild-to-moderate: No dose adjustment required
  • Severe (TB >3 x 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 next dose
    • Permanently discontinue for ≥grade 2 thrombocytopenia requiring a treatment delay ≥16 weeks
  • 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 next dose
    • Permanently discontinue for ≥grade 3 thrombocytopenia requiring a treatment delay ≥16 weeks
  • Grade 3 or 4 recurrence
    • Permanently discontinue

Renal toxicity

  • Renal toxicity definition
    • CrCl <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 next dose
    • Permanently discontinue for renal toxicity requiring a treatment delay ≥16weeks

Hepatotoxicity

  • Hepatotoxicity definition
    • Bilirubinemia >3x ULN (Grade 3 or 4) OR
    • Hypoalbuminemia <30 g/L with a decreased prothrombin ratio <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 next dose
    • Permanently discontinue for hepatotoxicity requiring a treatment delay ≥16weeks

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 next dose
    • Permanently discontinue for ≥grade 3 toxicity requiring a treatment delay ≥16 weeks
  • Grade 3 or 4 recurrence
    • Permanently discontinue

Dosing Considerations

Verify pregnancy status of females of reproductive potential prior to initiating

Safety and efficacy not established

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Interactions

Interaction Checker

and lutetium Lu 177-dota-tate

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            Adverse Effects

            >10% All Grades

            Lymphopenia (90%)

            Creatinine increased (85%)

            Hyperglycemia (82%)

            Anemia (81%)

            Increased GGT (66%)

            Increased alkaline phosphatase (65%)

            Nausea (65%)

            Leukopenia (55%)

            Vomiting (53%)

            Thrombocytopenia (53%)

            AST increased (50%)

            ALT increased (43%)

            Fatigue (38%)

            Hyperuricemia (34%)

            Hypocalcemia (32%)

            Blood bilirubin increased (30%)

            Hypokalemia (26%)

            Abdominal pain (26%)

            Diarrhea (26%)

            Neutropenia (26%)

            Decreased appetite (21%)

            Hyperkalemia (19%)

            Hypernatremia (17%)

            Headache (17%)

            Dizziness (17%)

            Peripheral edema (16%)

            Hypoglycemia (15%)

            Flushing (14%)

            Back pain (13%)

            Anxiety (12%)

            Renal failure (12%)

            Alopecia (12%)

            Hypertension (12%)

            Pain in extremity (11%)

            Cough (11%)

            >10% Grades 3-4

            Lymphopenia (44%)

            Increased GGT (20%)

            1-10% All Grades

            Constipation (10%)

            Pyrexia (8%)

            Dysgeusia (8%)

            Radiation-related toxicity to urinary tract (8%)

            Atrial fibrillation (5%)

            Myalgia (5%)

            Neck pain (5%)

            1-10% Grades 3-4

            Vomiting (7%)

            Hyperuricemia (6%)

            Nausea (5%)

            Alkaline phosphatase increased (5%)

            AST increased (5%)

            ALT increased (4%)

            Hyperglycemia (4%)

            Hypokalemia (4%)

            Renal failure (3%)

            Abdominal pain (3%)

            Diarrhea (3%)

            Neutropenia (3%)

            Back pain (2%)

            Hypertension (2%)

            Leukopenia (2%)

            Blood bilirubin increased (2%)

            Anxiety (1%)

            Atrial fibrillation (1%)

            Fatigue (1%)

            Cough (1%)

            Thrombocytopenia (1%)

            Creatinine increased (1%)

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            Warnings

            Contraindications

            None

            Cautions

            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 (see Dosage Modifications)

            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 (see Adult Dosing and Dosage Modifications)

            Rare reports of hepatotoxicity; monitor transaminases, bilirubin, and serum albumin (see Dosage Modifications)

            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 (see Pregnancy)

            Drug interaction overview

            • Somatostatin and its analogs competitively bind to somatostatin receptors and may interfere with lutetium Lu 177-dota-tate efficacy (see Adult Dosing)
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            Pregnancy

            Pregnancy

            Based on its mechanism of action, can cause fetal harm and infertility

            No data are available regarding use in pregnant women; however, all radiopharmaceuticals have the potential to cause fetal harm

            Advise pregnant women of the risk to a fetus

            Verify pregnancy status of females of reproductive potential prior to initiating

            Infertility

            • May cause infertility in males and females
            • The recommended cumulative dose of 29.6 GBq results in a radiation absorbed dose to the testis and ovaries within the range in which temporary or permanent infertility can be expected following external beam radiotherapy

            Contraception

            • Females: Advise females of reproductive potential to use effective contraception during treatment and for 7 months after the final dose
            • Males: Advise males with female partners of reproductive potential to use effective contraception during and for 4 months after the final dose

            Lactation

            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, advise women not to breastfeed during treatment and for 2.5 months after the final dose

            Pregnancy Categories

            A:Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

            B:May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

            C:Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

            D:Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

            X:Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

            NA:Information not available.

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            Pharmacology

            Mechanism of Action

            Radiolabeled somatostatin analog; binds to somatostatin receptors with highest affinity for subtype 2 receptors (SSRT2)

            Upon binding to somatostatin receptor-expressing cells, including malignant somatostatin receptor-positive tumors, the compound is internalized

            Beta emission from Lu 177 induces cellular damage by forming free radicals in somatostatin receptor-positive cells and in neighboring cells

            Absorption

            Peak plasma concentration: 10 ng/mL (mean) at end of IV infusion

            AUC: 41 n·gh/mL (mean)

            Distribution

            Protein bound: 43%

            Vd: 640 L; within 4 hr drug is distributed in kidneys, tumor lesions, liver, spleen, and in some patients, pituitary and thyroid glands

            Coadministration of amino acids reduces median radiation dose to the kidneys by 47% (34-59%) and increases mean beta-phase blood clearance by 36%

            Metabolism

            Does not undergo hepatic metabolism

            Elimination

            Half-life, blood elimination: 3.5 hr

            Half-life, terminal: 71 hr

            Clearance: 4.5 L/hr

            Excretion

            • Primarily eliminated renally
            • 44% within 5 hr after dose
            • 58% within 24 hr after dose
            • 65% within 48 hr after dose
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            Administration

            IV Preparation

            Use aseptic technique and radiation shielding when administering solution

            Use tongs when handling vial to minimize radiation exposure

            Do not inject directly into any other IV solution

            Confirm the amount of radioactivity in the radiopharmaceutical vial with an appropriate dose calibrator prior to and after administration

            Inspect the product visually for particulate matter and discoloration under a shielded screen prior to administration; solution should appear clear and colorless to slightly yellow; discard vial if particulates or discoloration are present

            Handling radiopharmaceuticals

            • Radiopharmaceutical; handle with appropriate safety measures to minimize radiation exposure
            • Use waterproof gloves and effective radiation shielding when handling
            • Radiopharmaceuticals should be used by or under the control of physicians who are qualified by specific training and experience in the safe use and handling, and whose experience and training have been approved by the appropriate governmental agency authorized to license the use of radiopharmaceuticals

            IV Administration

            Insert a 2.5-cm, 20-gauge needle (short needle) into the lutetium Lu 177-dota-tate vial and connect via a catheter to 500 mL 0.9% NaCl solution

            Ensure that the short needle does not touch the lutetium Lu 177-dota-tate solution in the vial and do not connect this short needle directly to the patient

            Do not allow 0.9% NaCl solution to flow into the lutetium Lu 177-dota-tate vial prior to the initiation of the infusion and do not inject lutetium Lu 177-dota-tate directly into the 0.9% NaCl solution

            Insert a second needle that is 9 cm, 18 gauge (long needle) into the lutetium Lu 177-dota-tate vial, ensuring that this long needle touches and is secured to the bottom of the vial during the entire infusion

            Connect the long needle to the patient by an IV catheter that is prefilled with 0.9% NaCl and that is used exclusively for the lutetium Lu 177-dota-tate infusion into the patient

            Use a clamp or pump to regulate the flow of the 0.9% NaCl solution via the short needle into the lutetium Lu 177-dota-tate vial at a rate of 50-100 mL/hr for 5-10 minutes and then 200-300 mL/hr for an additional 25-30 minutes

            The 0.9% NaCl solution entering the vial through the short needle will carry the lutetium Lu 177-dota-tate from the vial to the patient via the catheter connected to the long needle over a total duration of 30-40 minutes

            Do not administer lutetium Lu 177-dota-tate as an IV

            During the infusion, ensure that the level of solution in the lutetium Lu 177-dota-tate vial remains constant

            Disconnect the vial from the long needle line and clamp the saline line once the level of radioactivity is stable for at least 5 minutes

            Follow the infusion with an IV flush of 25 mL of 0.9% NaCl

            Dispose of any unused medicinal product or waste material in accordance with local and federal laws

            Storage

            Store in the original package (ie, lead-shielded container placed in a plastic sealed container)

            Store at temperature below 25°C (77°F)

            Shelf life is 72 hr; discard appropriately at 72 hr

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            Formulary

            FormularyPatient Discounts

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            The above information is provided for general informational and educational purposes only. Individual plans may vary and formulary information changes. Contact the applicable plan provider for the most current information.

            Tier Description
            1 This drug is available at the lowest co-pay. Most commonly, these are generic drugs.
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            3 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs.
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            5 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
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            NC NOT COVERED – Drugs that are not covered by the plan.
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