10/22. Lutetium (PLUVICTO) (Mar 2022)- To treat Prostrate Specific Membraine Antigen Positive Metastatic Castration Resistent Cancer
Indication:
BRIEF SUMMARY-
LUTETIUM-(Mar 2022)
Indn- To treat prostrate _Specific Membrane Antigen Positive Metastatic Castration Resistent Cancer Following Other therapies
Dosage- Injection: 1,000 MBq/mL (27 mCi/mL) in a single-dose vial. Recommended Dosage: Administer 7.4 GBq (200 mCi) every 6 weeks for up to 6 doses.
ADR- Most common adverse reactions (= 20%) are fatigue, dry mouth, nausea,anemia, decreased appetite, and constipation.
CI- None.
WARNINGS-
Risk From Radiation Exposure: Minimize radiation exposure during and after treatment with institutional good radiation safety practices and patient treatment procedures. Ensure patients increase oral fluid intake and advise patients to void as often as possible to reduce bladder radiation.
Myelosuppression: Perform complete blood counts. Withhold, reduce dose,
or permanently discontinue and clinically treat based on severity.
Pat Inform-
Ensure patients increase oral fluid intake and advise patients to void as often as possible to reduce bladder radiation
Following administration, advise patients to limit close contact (less than
3 feet) with household contacts for 2 days or with children and pregnant women for 7 days
advise patients to refrain from sexual activity for 7 days. advise patients to sleep in a separate bedroom from household contacts for 3 days, from children
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U.S. FDA APPROVED DRUGS SURING 2022
Serial No 10
Name of the Drug- PLUVICTO
Active Ingredient - Lutetium Uipivotide Tetraxetan
Pharmacological Classification- To treat prostrate _Specific Membrane Antigen Positive Metastatic Castration Resistent Cancer Following Other therapies
Date of Approval- 3/23/22
HIGHLIGHTS OF PRESCRIBING INFORMATION
These highlights do not include all the information needed to use PLUVICTO safely and effectively. See full prescribing information for PLUVICTO. PLUVICTOTM (lutetium Lu 177 vipivotide tetraxetan) injection, for intravenous use
Initial U.S. Approval: 2022
INDICATIONS AND USAGE-
PLUVICTO is a radioligand therapeutic agent indicated for the treatment of adult patients 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.
Adverse Reaction:
ADVERSE REACTIONS-
Most common adverse reactions (= 20%) are fatigue, dry mouth, nausea,
anemia, decreased appetite, and constipation.
Most common laboratory abnormalities (= 30%) are decreased lymphocytes,
decreased hemoglobin, decreased leukocytes, decreased platelets, decreased
calcium, and decreased sodium.
Contra-Indications:
CONTRAINDICATIONS- None.
WARNINGS AND PRECAUTIONS-
• Risk From Radiation Exposure: Minimize radiation exposure during and after treatment with PLUVICTO consistent with institutional good radiation safety practices and patient treatment procedures. Ensure patients increase oral fluid intake and advise patients to void as often as possible to reduce bladder radiation.
• Myelosuppression: Perform complete blood counts. Withhold, reduce dose,
or permanently discontinue PLUVICTO and clinically treat based on
severity.
• Renal Toxicity: Advise patients to remain well hydrated and to urinate
frequently. Perform kidney function laboratory tests. Withhold, reduce
dose, or permanently discontinue PLUVICTO based on severity. \
• Embryo-Fetal Toxicity: Can cause fetal harm. Advise male patients with
female partners of reproductive potential to use effective contraception.
• Infertility: PLUVICTO may cause temporary or permanent infertility.
Dosages/ Overdosage Etc:
DOSAGE AND ADMINISTRATION-
• Select patients for treatment using LOCAMETZ® or an approved PSMA-11 imaging agent based on PSMA expression in tumors.
• Recommended Dosage: Administer 7.4 GBq (200 mCi) every 6 weeks for up to 6 doses.
• Dose interruption, reduction, or permanent discontinuation may be required due to adverse reactions.
DOSAGE FORMS AND STRENGTHS-
Injection: 1,000 MBq/mL (27 mCi/mL) in a single-dose vial.
Patient Information:
PATIENT COUNSELING INFORMATION
Risk From Radiation Exposure
Ensure patients increase oral fluid intake and advise patients to void as often as possible to reduce bladder radiation [see
Warnings and Precautions-
Explain the necessary radioprotection precautions that the patient should follow to minimize radiation exposure to others before the patient is released. Following administration of PLUVICTO, advise patients to limit close contact (less than
3 feet) with household contacts for 2 days or with children and pregnant women for 7 days
Following administration of PLUVICTO, advise patients to refrain from sexual activity for 7 days. Following administration of PLUVICTO, advise patients to sleep in a separate bedroom from household contacts for 3 days, from children
Myelosuppression
Advise patients to contact their healthcare provider for any signs or symptoms of myelosuppression, such as 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
Advise patients to remain well hydrated and to urinate frequently before and after administration of PLUVICTO. Advise patients to contact their healthcare provider for any signs or symptoms of renal toxicity, such as passing urine less often than usual or passing much smaller amounts of urine than usual .
Embryo-Fetal Toxicity
Advise patients that PLUVICTO can cause fetal harm
Use in Specific Populations
Advise male patients with female partners of reproductive potential to use effective contraception during treatment with PLUVICTO and for 14 weeks after the last dose ,
Infertility-
Advise males of reproductive potential that PLUVICTO may cause temporary or permanent infertility
Distributed by:
Advanced Accelerator Applications USA, Inc.
Millburn, NJ 07041
©2022 Advanced Accelerator Applications USA, Inc.
PLUVICTO is a trademark of Novartis AG and/or its affiliates
U.S. Patents 10398791; 10406240
Reference ID:
Pharmacology/ Pharmacokinetics:
CLINICAL PHARMACOLOGY
1 Mechanism of Action
Lutetium Lu 177 vipivotide tetraxetan is a radioligand therapeutic agent. The active moiety of lutetium Lu 177 vipivotide tetraxetan is the radionuclide lutetium-177 which is linked to a moiety that binds to PSMA, a transmembrane protein that is expressed in prostate cancer, including mCRPC. Upon binding of lutetium Lu 177 vipivotide tetraxetan to PSMAexpressing cells, the beta-minus emission from lutetium-177 delivers radiation to PSMA-expressing cells, as well as to surrounding cells, and induces DNA damage which can lead to cell death.
2. Pharmacodynamics
Lutetium Lu 177 vipivotide tetraxetan exposure-efficacy relationships and the time course of pharmacodynamic response have not been fully characterized.
Cardiac Electrophysiology
At the recommended dosage, PLUVICTO does not cause large mean increases (> 20 ms) in the QTc interval.
3. Pharmacokinetics
Pharmacokinetics of lutetium Lu 177 vipivotide tetraxetan are expressed as geometric mean (geometric mean coefficient of variation) unless otherwise specified.
The blood lutetium Lu 177 vipivotide tetraxetan area under the curve (AUC) is 52.3 ng.h/mL (31.4%) and the maximum blood concentration is 6.58 ng/mL (43.5%) at the recommended dosage.
Distribution
Lutetium Lu 177 vipivotide tetraxetan volume of distribution is 123 L (78.1%).
Within 2.5 hours of administration, lutetium Lu 177 vipivotide tetraxetan distributes to gastrointestinal tract, liver, lungs,kidneys, heart wall, bone marrow, and salivary glands.
Vipivotide tetraxetan and non-radioactive lutetium vipivotide tetraxetan are 60% to 70% bound to human plasma proteins.
Elimination
The lutetium Lu 177 vipivotide tetraxetan terminal elimination half-life is 41.6 hours (68.8%) and the clearance (CL) is 2.04 L/h (31.5%).
Excretion
Lutetium Lu 177 vipivotide tetraxetan is primarily eliminated renally.
Specific Populations
Exposure (AUC) of lutetium Lu 177 vipivotide tetraxetan increased with decreasing creatinine clearance (CLcr). The effect of baseline CLcr < 54 mL/min on lutetium Lu 177 vipivotide tetraxetan pharmacokinetics has not been studied.
Drug Interaction Studies
In Vitro Studies
CYP450 enzymes: Vipivotide tetraxetan is not a substrate of cytochrome P450 (CYP450) enzymes. Vipivotide tetraxetan did not induce CYP1A2, 2B6 or 3A4; and did not inhibit CYP1A2, 2B6, 2C8, 2C9, 2C19, 2D6 or 3A in vitro.
Transporters: Vipivotide tetraxetan is not a substrate of BCRP, P-gp, MATE1, MATE2-K, OAT1, OAT3 or OCT2.
Vipivotide tetraxetan did not inhibit BCRP, P-gp, MATE1, MATE2-K, OAT1, OAT3, OATP1B1, OATP1B3, OCT1 or OCT2 in vitro.
Pregnancy and lactation:
USE IN SPECIFIC POPULATIONS
1 Pregnancy
Risk Summary
The safety and efficacy of PLUVICTO have not been established in females. Based on its mechanism of action,
PLUVICTO can cause fetal harm [see Clinical Pharmacology. There are no available data on PLUVICTO use in pregnant females. No animal studies using lutetium Lu 177 vipivotide tetraxetan have been conducted to evaluate it effect on female reproduction and embryo-fetal development; however, all radiopharmaceuticals, including PLUVICTO,have the potential to cause fetal harm.
2, Lactation
Risk Summary
The safety and efficacy of PLUVICTO have not been established in females. There are no data on the presence of lutetium Lu 177 vipivotide tetraxetan in human milk or its effects on the breastfed child or on milk production.
3, Females and Males of Reproductive Potential
Contraception- Males
Based on its mechanism of action, advise male patients with female partners of reproductive potential to use effective contraception during treatment with PLUVICTO and for 14 weeks after the last dose.
Nonclinical Toxicology (13.1)].
Infertility
The recommended cumulative dose of 44.4 GBq of PLUVICTO results in a radiation absorbed dose to the testes within the range where PLUVICTO may cause temporary or permanent infertility.
4. Pediatric Use
The safety and effectiveness of PLUVICTO in pediatric patients have not been established.
5. Geriatric Use
Of the 529 patients who received at least one dose of PLUVICTO plus BSoC in the VISION study, 387 patients (73%) were 65 years or older and 143 patients (27%) were 75 years or older. No overall differences in effectiveness were observed between patients = 75 years of age and younger patients. Serious adverse reactions occurred in 11% of patients = 75 years of age and in 11% of younger patients. Grade = 3 adverse reactions occurred in 40% of patients = 75 years of age and in 31% of younger patients.
6. Renal Impairment
Exposure of lutetium Lu 177 vipivotide tetraxetan is expected to increase with the degree of renal impairment . No dose adjustment is recommended for patients with mild (baseline CLcr 60 to 89 mL/min by Cockcroft-Gault) to moderate (CLcr 30 to 59 mL/min) renal impairment; however, patients with mild or moderate renal impairment may be at greater risk of toxicity. Frequently monitor renal function and adverse reactions in
patients with mild to moderate renal impairment. The pharmacokinetics and safety
of PLUVICTO have not been studied in patients with severe (CLcr 15 to 29 mL/min) renal impairment or end-stage renal
disease.
OVERDOSAGE
In the event of administration of a radiation overdosage with PLUVICTO, reduce the radiation absorbed dose to the patient by increasing the elimination of the radionuclide from the body by frequent micturition or by forced diuresis and frequent bladder voiding. Estimate the effective radiation dose that was applied and treat with additional supportive care measures as clinically indicated.
