lutetium Lu 177 vipivotide tetraxetan (Rx)

Brand and Other Names:Pluvicto

Dosing & Uses

AdultPediatric

Dosage Forms & Strengths

injection, solution for IV use

  • 1,000 MBq/mL (27 mCi/mL) single-dose vial

Castration-Resistant Prostate Cancer

Indicated for the treatment of men with prostate-specific membrane antigen (PSMA)-positive, metastatic castration-resistant prostate cancer (mCRPC) who have been treated with androgen receptor (AR) pathway inhibition and taxane-based chemotherapy

7.4 GBq (200 mCi) IV q6Weeks for up to 6 doses, or until disease progression, or unacceptable toxicity

Dosage Modifications

General recommendations

  • Management of adverse reactions may require temporary dose interruption (extending the dosing interval from q6Weeks up to q10Weeks), dose reduction, or permanent discontinuation
  • If treatment delay persists for >4 weeks, treatment must be discontinued
  • Dose may be reduced by 20% to 5.9 GBq (160 mCi) once; do not re-escalate dose
  • If further adverse reactions occur that would require an additional dose reduction, treatment must be discontinued

Myelosuppression

  • Anemia, thrombocytopenia, leukopenia, or neutropenia
  • Grade 2: Withhold until improvement to Grade 1 or baseline
  • Grade ≥3: Withhold until improvement to Grade 1 or baseline, reduce dose by 20% to 5.9 GBq (160 mCi)
  • Recurrent Grade >3 myelosuppression after 1 dose reduction: Permanently discontinue

Renal toxicity

  • Withhold until improvement
    • Confirmed serum creatinine increase (Grade ≥2)
    • Confirmed CrCl <30mL/min; calculate using Cockcroft-Gault equation with actual body weight
  • Withhold until improvement/baseline and reduce dose by 20%
    • CrCl confirmed increase ≥40% from baseline AND
    • CrCl confirmed >40% decrease from baseline; calculate using Cockcroft-Gault equation with actual body weight
Permanently discontinue
  • Grade ≥3
  • Recurrent renal toxicity after 1 dose reduction

Dry mouth

  • Grade 2: Withhold until improvement or return to baseline, consider reducing dose by 20%
  • Grade 3: Withhold until improvement or return to baseline, reduce dose by 20% to 5.9 GBq (160 mCi)
  • Recurrent Grade 3 dry mouth after 1 dose reduction: Permanently discontinue

Gastrointestinal (GI) toxicity

  • Grade ≥3
    • Not amenable to medical intervention: Withhold until improvement to Grade 2 or baseline, reduce dose by 20% to 5.9 GBq (160 mCi)
    • Recurrent Grade ≥3 GI toxicity after 1 dose reduction: Permanently discontinue

Fatigue

  • Grade ≥3: Withhold until improvement to Grade 2 or baseline

Electrolyte or metabolic abnormalities

  • Grade ≥2: Withhold until improvement to Grade 1 or baseline

Elevated AST/AST

  • AST or ALT >5X ULN in absence of liver metastases: Permanently discontinue

Other nonhematologic toxicity

  • Permanently discontinue for
    • Any unacceptable toxicity
    • Any serious adverse reaction requiring treatment delay of >4 weeks
    • Any recurrent Grade 3 or 4 or persistent and intolerable Grade 2 adverse reactions after 1 dose reduction

Renal impairment

  • Mild-to-moderate (CrCl 30-89 mL/min): No dosage adjustment recommended; but frequently monitor kidney function and adverse reactions, as this group of patients may be at great risk of toxicity
  • Severe (CrCl 15-29 mL/min) or end-stage renal disease: Not studied

Hepatic impairment

  • No data are available

Dosing Considerations

Patient selection: Select patients with previously treated mCRPC using LOCAMETZ or another approved PSMA-11 imaging agent based on PSMA expression in tumors

Safety and efficacy not established

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Adverse Effects

>10%

All grades

  • Decreased lymphocytes (85%)
  • Decreased hemoglobin (63%)
  • Decreased leukocytes (56%)
  • Decreased platelets (45%)
  • Fatigue (43%)
  • Dry mouth (39%)
  • Decreased calcium (39%)
  • Nausea (35%)
  • Decreased sodium (33%)
  • Anemia (32%)
  • Increased AST (28%)
  • Decreased neutrophils (28%)
  • Increased creatinine (24%)
  • Increased potassium (24%)
  • Decreased appetite (21%)
  • Constipation (20%)
  • Vomiting (19%)
  • Diarrhea (19%)
  • Thrombocytopenia (17%)
  • Urinary tract infection (12%)
  • Weight loss (11%)
  • Abdominal pain (11%)
  • Increased sodium (11%)

Grades 3-4

  • Decreased lymphocytes (47%)
  • Decreased hemoglobin (15%)
  • Anemia (13%)

1-10%

All grades

  • Peripheral edema (10%)
  • Acute kidney injury (9%)
  • Dizziness (8%)
  • Headache (7%)
  • Dysgeusia (7%)
  • Pyrexia (7%)

Grades 3-4

  • Decreased platelets (9%)
  • Thrombocytopenia (8%)
  • Decreased leukocytes (7%)
  • Fatigue (6%)
  • Decreased neutrophils (4.5%)
  • Urinary tract infection (3.8%)
  • Acute kidney injury (3.2%)
  • Decreased calcium (2.5%)
  • Decreased appetite (1.9%)
  • Nausea (1.3%)
  • Constipation (1.1%)
  • Abdominal pain (1.1%)
  • Increased AST (1.1%)

<1%

Grades 3-4

  • Weight loss
  • Peripheral edema
  • Pyrexia
  • Vomiting
  • Diarrhea
  • Dizziness
  • Headache
  • Decreased sodium
  • Increased creatinine
  • Increased potassium
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Warnings

Contraindications

None

Cautions

Based on its mechanism of action, can cause fetal harm

May cause temporary or permanent infertility in males

Radiation exposure

  • Contributes to patient’s overall long-term cumulative radiation exposure
  • Long-term cumulative radiation exposure is associated with increased risk for cancer
  • Minimize radiation exposure to patients, medical personnel, and household contacts during and after treatment
  • Ensure that patients increase oral fluid intake and advise patients to void as often as possible to reduce bladder radiation
  • Before patient is released, explain necessary radioprotection precautions to follow to minimize radiation exposure to others
  • Advise patient to limit close contact (<3 feet) with household contacts for 2 days or with children and pregnant women for 7 days
  • Advise patient to refrain from sexual activity for 7 days, and to sleep in a separate bedroom from household contacts for 3 days, from children for 7 days, or from pregnant women for 15 days

Myelosuppression

  • My cause severe and life-threatening myelosuppression, including anemia, thrombocytopenia, leukopenia, and neutropenia
  • Perform complete blood cell counts before and during treatment
  • Withhold, reduce dose, or permanently discontinue and clinically treat patients based on the severity of myelosuppression
  • Advise patients to contact their healthcare provider for any signs or symptoms of myelosuppression (eg, tiredness, weakness, pale skin, shortness of breath, bleeding or bruising more easily than normal, or difficulty to stop bleeding) or frequent infections with signs, such as fever, chills, sore throat, or mouth ulcers

Renal toxicity

  • Can cause severe renal toxicity
  • Advise patients to remain well hydrated and to urinate frequently before and after administration
  • Perform kidney function laboratory tests, including serum creatinine and calculated CrCl, before and during treatment
  • Withhold, reduce dose, or permanently discontinue based on severity of renal toxicity
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Pregnancy & Lactation

Pregnancy

Data are not available on use in pregnant females; based on its mechanism of action, can cause fetal harm

No animal studies have been conducted to evaluate its effect on female reproduction and embryo-fetal development; however, all radiopharmaceuticals have potential to cause fetal harm

Contraception

  • Based on its mechanism of action, advise male patients with female partners of reproductive potential to use effective contraception during treatment and for 14 weeks after the last dose

Infertility

  • Cumulative dose of 44.4 GBq results in a radiation absorbed dose to the testes within the range that may cause temporary or permanent infertility

Lactation

There are no data on presence in human milk or its effects on breastfed children or milk production

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

Radioligand therapeutic agent; active moiety is the radionuclide lutetium-177, which is linked to a moiety that binds to PSMA, a transmembrane protein expressed in prostate cancer, including mCRPC

Upon binding to PSMA-expressing cells, lutetium-177 delivers beta-minus radiation to PSMA-expressing cells, as well as to surrounding cells, and induces DNA damage that can lead to cell death

Absorption

Peak plasma concentration: 6.58 ng/mL

AUC: 52.3 ng⋅hr/mL

Distribution

Protein bound: 60-70%

Vd: 123 L

Within 2.5 hr of administration, distributes to gastrointestinal tract, liver, lungs, kidneys, heart wall, bone marrow, and salivary glands

Elimination

Half-life: 41.6%

Clearance: 2.04 L/hr

Excretion: Primarily eliminated renally

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Administration

IV Preparation

Use aseptic technique and radiation shielding when handling or administering, using tongs as needed to minimize radiation exposure

Inspect vial visually under a shielded screen for particulate matter and discoloration before administration

Discard vial if particulates or discoloration observed

Do not inject solution directly into any other IV solution

Confirm amount of radioactivity delivered to the patient with an appropriately calibrated dose calibrator before and after administration

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

Radiopharmaceutical safety instructions

  • 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 healthcare providers 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

IV Administration

May be administered IV as an injection using a disposable syringe fitted with syringe shield (with or without a syringe pump), as an infusion using gravity method (with or without an infusion pump), or as an infusion using the vial (with a peristaltic infusion pump)

Reduced dose: Use syringe method (with or without syringe pump); gravity method not recommended since it may result in delivery of the incorrect volume, if the dose is not adjusted prior to administration

Before administration, flush IV catheter used exclusively for lutetium Lu 177 vipivotide tetraxetan administration with >10 mL 0.9% NaCl to ensure patency and minimize extravasation risk (manage extravasation per institutional guidelines)

See prescribing information for precise instructions for each administration method (ie, syringe, gravity, vial)

Storage

Store below 30ºC (86ºF); do not freeze

Store in original package to protect from ionizing radiation (lead shielding)

Shelf-life is 120 hr (5 days) from date and time of calibration

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Images

No images available for this drug.
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Patient Handout

A Patient Handout is not currently available for this monograph.
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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.
2 This drug is available at a middle level co-pay. Most commonly, these are "preferred" (on formulary) brand drugs.
3 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs.
4 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
5 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
6 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
NC NOT COVERED – Drugs that are not covered by the plan.
Code Definition
PA Prior Authorization
Drugs that require prior authorization. This restriction requires that specific clinical criteria be met prior to the approval of the prescription.
QL Quantity Limits
Drugs that have quantity limits associated with each prescription. This restriction typically limits the quantity of the drug that will be covered.
ST Step Therapy
Drugs that have step therapy associated with each prescription. This restriction typically requires that certain criteria be met prior to approval for the prescription.
OR Other Restrictions
Drugs that have restrictions other than prior authorization, quantity limits, and step therapy associated with each prescription.
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Medscape prescription drug monographs are based on FDA-approved labeling information, unless otherwise noted, combined with additional data derived from primary medical literature.