Dosing & Uses
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
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
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
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.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
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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