Lutetium Lu 177 vipivotide tetraxetan

Lutetium Lu 177 vipivotide tetraxetan is a radioligand therapy used for a specific type of advanced prostate cancer. Radioligand therapy is a targeted radiation treatment in which a radioactive chemical (radionuclide) is administered as an intravenous (IV) injection. Radioligand therapy is used to specifically target the cancer cells and kill them, and limit the harm to normal cells that can result from traditional radiation therapies.

Lutetium Lu 177 vipivotide tetraxetan is used to treat prostate-specific membrane antigen (PSMA)-positive, metastatic castration-resistant prostate cancer (mCRPC). These advanced metastatic prostate cancers do not respond to chemotherapy or treatments that lower testosterone. PSMA is a prostate-specific protein that is present in great amounts in the membranes of the cancer cells.

Lutetium Lu 177 vipivotide tetraxetan is a radioconjugate drug that contains vipivotide tetraxetan, a substance (ligand) that identifies and binds to PSMA on the cancer cells. The radionuclide lutetium Lu 177 then delivers radiation to the PSMA-expressing cells and the surrounding cells and destroys them.

• Lutetium Lu 177 vipivotide tetraxetan can cause fetal harm
• May cause temporary or permanent infertility in males
• Lutetium Lu 177 vipivotide tetraxetan contributes to the patient’s overall long-term cumulative radiation exposure, which increases the risk for cancer
• Minimize radiation exposure to patients, medical personnel, and household contacts during and after treatment
• Before patient is released, explain necessary radioprotection precautions to follow to minimize radiation exposure to others:
  • Patient must avoid close contact (less than 3 feet) for 2 days with others at home and for 7 days with children and pregnant women 
  • Patient must refrain from sexual activity for 7 days
  • Patient must sleep in a separate bedroom from other adults for 3 days, from children for 7 days, and from pregnant women for 15 days
• Lutetium Lu 177 vipivotide may cause severe and life-threatening bone marrow suppression (myelosuppression) that can result in anemia, thrombocytopenia, leukopenia, and neutropenia
• Perform complete blood cell counts before and during treatment and titrate the dose accordingly or discontinue therapy 
• Advise patients to contact their healthcare provider in case of myelosuppression symptoms of (e.g., tiredness, weakness, pale skin, shortness of breath, bleeding or bruising more easily than normal, or difficulty in stopping bleeding) or frequent infections with signs such as fever, chills, sore throat, or mouth ulcers
• Can be severely toxic to the kidney; ensure that patients increase oral fluid intake and advise patients to urinate as often as possible to reduce bladder radiation
• Perform kidney function tests before and during treatment and adjust dosage accordingly or discontinue therapy based on severity of renal toxicity

Common side effects of lutetium Lu 177 vipivotide tetraxetan include:

• All grades
• Decrease in lymphocytes
• Decrease in hemoglobin
• Decrease in leukocytes
• Decrease in platelets
• Decrease in neutrophils
• Low red blood cell count (anemia)
• Decrease in calcium
• Decrease in sodium
• Increase in potassium
• Increase in liver enzyme AST
• Increase in creatinine
• Fatigue
• Dry mouth
• Nausea
• Decrease in appetite
• Constipation
• Vomiting
• Diarrhea
• Weight loss
• Abdominal pain
• Low platelet count (thrombocytopenia)
• Urinary tract infection
• Increase in sodium

Grades 3-4

• Decreased lymphocytes
• Decreased hemoglobin
• Anemia

Less common side effects of lutetium Lu 177 vipivotide tetraxetan include:

All grades

• Swelling of extremities (peripheral edema)
• Acute kidney injury
• Dizziness
• Headache
• Taste perversion (dysgeusia)
• Fever (pyrexia)

Grades 3-4

• Decrease in platelets
• Thrombocytopenia
• Decrease in leukocytes
• Fatigue
• Decrease in neutrophils
• Urinary tract infection
• Acute kidney injury
• Decrease in calcium
• Decrease in appetite
• Nausea
• Constipation
• Abdominal pain
• Increase in AST

Rare side effects of lutetium Lu 177 vipivotide tetraxetan include:

• Grades 3-4
• Weight loss
• Peripheral edema
• Pyrexia
• Vomiting
• Diarrhea
• Dizziness
• Headache
• Decrease in sodium
• Increase in creatinine
• Increase in potassium

This is not a complete list of all side effects or adverse reactions that may occur from the use of this drug.

Call your doctor for medical advice about serious side effects or adverse reactions. You may also report side effects or health problems to the FDA at 1-800-FDA-1088.

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 every 6 weeks 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 every 6 weeks up to every 10 weeks), dose reduction, or permanent discontinuation
• If treatment delay persists for longer than 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 or higher: 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 or higher)
  • Confirmed creatinine clearance (CrCl) higher than 30mL/minute; calculate using Cockcroft-Gault equation with actual body weight
• Withhold until improvement/baseline and reduce dose by 20%
  • CrCl confirmed increase 40% or higher from baseline AND
  • CrCl confirmed higher than 40% decrease from baseline; calculate using Cockcroft-Gault equation with actual body weight
• Permanently discontinue
  • Grade 3 or higher
  • 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 or higher
• 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 or higher GI toxicity after 1 dose reduction: Permanently discontinue

Fatigue

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

Electrolyte or metabolic abnormalities

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

Elevated AST/AST

• AST or ALT more than 5 times 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/minute): 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/minute) 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

• In case of radiation overdosage with lutetium Lu 177 vipivotide tetraxetan, the radiation absorbed dose is reduced by increasing the excretion of the radionuclide with increased urine output through diuresis.
• Based on the effective radiation dose that was applied, overdose is treated with additional supportive care measures.

Inform your doctor of all medications you are currently taking, who can advise you on any possible drug interactions. Never begin taking, suddenly discontinue, or change the dosage of any medication without your doctor’s recommendation.

• Severe interactions of lutetium Lu 177 vipivotide tetraxetan include:
  • abrocitinib
  • baricitinib
  • BCG products
  • dengue tetravalent vaccine
  • natalizumab
  • poliovirus vaccine (live/trivalent/oral)
  • rubella/varicella live vaccines
  • ruxolitinib
  • tacrolimus
  • typhoid vaccine
  • upadacitinib
  • live vaccines
  • yellow fever vaccine
• Lutetium Lu 177 vipivotide tetraxetan has serious interactions with at least 13 different drugs.
• Lutetium Lu 177 vipivotide tetraxetan has moderate interactions with at least 15 different drugs.
• Lutetium Lu 177 vipivotide tetraxetan has no known minor interactions.

The drug interactions listed above are not all of the possible interactions or adverse effects. For more information on drug interactions, visit the RxList Drug Interaction Checker.

It is important to always tell your doctor, pharmacist, or health care provider of all prescription and over-the-counter medications you use, as well as the dosage for each, and keep a list of the information.

Check with your doctor or health care provider if you have any questions about the medication.

• Increase oral fluid intake and urine output as much as possible to reduce the risk of bladder radiation
• Follow all the precautions during and after treatment as advised by your healthcare provider to minimize radiation exposure to others
• Seek medical help immediately in case of symptoms such as fatigue, weakness, shortness of breath, bleeding disorders, or frequent infections

• There are no animal reproduction studies, however, based on the mechanism of action, all radiopharmaceutical agents including lutetium Lu 177 vipivotide tetraxetan can cause fetal harm.
• Pregnant persons should avoid close contact (less than three feet) with patients treated with lutetium Lu 177 vipivotide tetraxetan, for 7 days after the treatment, and in addition, avoid sleeping in the same room for 15 days after the treatment.
• Male patients with female partners of reproductive potential must use effective contraception during treatment and for 14 weeks after the last dose.
• Cumulative dose of 44.4 GBq may cause temporary or permanent infertility in males.
• There are no data on presence in breast milk or its effects on breastfed infants or milk production.