Lutetium (177lu) Vipivotide Tetraxetan: prescribing information – dosing, contraindications, interactions, side effects

Pluvicto in combination with androgen deprivation therapy (ADT) with or without androgen receptor (AR) pathway inhibition is indicated for the treatment of adult patients with progressive prostate-specific membrane antigen (PSMA)-positive metastatic castration-resistant prostate cancer (mCRPC) who have been treated with AR pathway inhibition and taxane-based chemotherapy (see section 5.1).

Important safety instructions

Pluvicto should be administered only by persons authorised to handle radiopharmaceuticals in designated clinical settings (see section 6.6) and after evaluation of the patient by a qualified physician.

Radiopharmaceuticals, including Pluvicto, should be used by or under the control of healthcare professionals 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 authorised to license the use of radiopharmaceuticals.

Patient identification

Patients should be identified for treatment by PSMA imaging.

Posology

The recommended treatment regimen of Pluvicto is 7 400 MBq intravenously every 6 weeks (±1 week) for up to a total of 6 doses, unless there is disease progression or unacceptable toxicity.

Medical castration with a gonadotropin-releasing hormone (GnRH) analogue should be continued during treatment in patients not surgically castrated.

Treatment monitoring
Laboratory tests should be performed before and during treatment with Pluvicto. Dosing may need to be modified based on the test results (see Table 1).
- Haematology (haemoglobin, white blood cell count, absolute neutrophil count, platelet count)
- Kidney function (serum creatinine, calculated creatinine clearance [CLcr])
- Liver function (alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, blood serum albumin, total blood bilirubin)

Dose modifications for adverse reactions
Recommended dose modifications of Pluvicto for adverse reactions are provided in Table 1.
Management of severe or intolerable adverse reactions may require temporary dose interruption, dose reduction or permanent discontinuation of treatment with Pluvicto. If a treatment delay due to an adverse reaction persists for >4 weeks, treatment with Pluvicto must be discontinued. The dose of Pluvicto may be reduced by 20% to 5 900 MBq once; the dose should not be re-escalated. If a patient has further adverse reactions that would require an additional dose reduction, treatment with Pluvicto must be discontinued.

Table 1
Recommended dose modifications of Pluvicto for adverse reactions

Adverse reaction
Severitya
Dose modification
Dry mouth
Grade 3
Reduce Pluvicto dose by 20% to 5 900 MBq.
Gastrointestinal toxicity
Grade ≥3 (not amenable to medical intervention)
Withhold Pluvicto until improvement to grade 2 or baseline.
Reduce Pluvicto dose by 20% to 5 900 MBq.
Myelosuppresion
(anaemia, thrombocytopenia, leukopenia, neutropenia, pancytopenia)
Grade 2
Withhold Pluvicto until improvement to grade 1 or baseline.
Manage as deemed appropriate. The use of growth factors is permitted but should be discontinued once improved to grade 1 or baseline. Checking haematinic levels (iron, B12 and folate) and providing supplementation is advocated. Transfusions may be given as clinically indicated.
Grade ≥3
Withhold Pluvicto until improvement to grade 1 or baseline.
Reduce Pluvicto dose by 20% to 5 900 MBq.
Renal toxicity
Defined as:
- Confirmed serum creatinine increase
(grade ≥2)
- Confirmed CLcr
<50 mL/min; calculate using Cockcroft-Gault with actual body weight
Withhold Pluvicto until improvement.
Defined as:
- Confirmed ≥40% increase from baseline serum creatinine and
- Confirmed >40% decrease from baseline
CLcr; calculate using
Cockcroft-Gault with actual body weight
Withhold Pluvicto until improvement or return to baseline.
Reduce Pluvicto dose by 20% to 5 900 MBq.
Recurrent renal toxicity
(grade ≥3)
Permanently discontinue Pluvicto.
Spinal cord compression
Any
Withhold Pluvicto until the compression has been adequately treated and any neurological sequela have stabilised and ECOG performance status has stabilised.
Fracture in weight-bearing bones Any
Withhold Pluvicto until the fracture has been adequately stabilised/treated and ECOG performance status has stabilised.
Fatigue
Grade ≥3
Withhold Pluvicto until improvement to
Grade 2 or baseline.
Electrolyte or metabolic abnormalities
Grade ≥2
Withhold Pluvicto until improvement to
Grade 1 or baseline.
Non-haematological toxicity (clinically significant, not otherwise stated)
Grade ≥2
Withhold Pluvicto until improvement to
Grade 1 or baseline.

AST or ALT elevation
AST or ALT >5 times ULN in the absence of liver metastases
Permanently discontinue Pluvicto.
Abbreviations: CLcr, creatinine clearance; ECOG, Eastern Cooperative Oncology Group; AST, aspartate aminotransferase; ALT, alanine aminotransferase; ULN, upper limit of normal.
Grading according to most current Common Terminology Criteria for Adverse Events (CTCAE).
a
The same thresholds are also applicable to baseline values at the time of treatment initiation with Pluvicto.

Special populations
Elderly
No dose adjustment is recommended in patients aged 65 years or older.

Renal impairment
No dose adjustment is recommended for patients with mild to moderate renal impairment with baseline CLcr ≥50 mL/min by Cockcroft-Gault. Treatment with Pluvicto is not recommended in patients with moderate to severe renal impairment with baseline CLcr <50 mL/min or end-stage renal disease as the pharmacokinetic profile and safety of Pluvicto have not been studied in these patients (see sections 4.4 and 5.2).

Hepatic impairment
No dose adjustment is recommended for patients with hepatic impairment. Pluvicto has not been studied in patients with moderate or severe hepatic impairment (see section 5.2).

Paediatric population
There is no relevant use of Pluvicto in the paediatric population in the indication of treatment of PSMA-expressing prostate cancer.

Method of administration

Pluvicto is a ready-to-use solution for injection/infusion for single use only.

Administration instructions
The recommended dose of Pluvicto may be administered intravenously as an injection using the syringe method, as an infusion using the gravity method, or as an infusion using the peristaltic pump method.

When using the gravity or peristaltic pump method, Pluvicto should be infused directly from its original container.

The syringe method or the peristaltic pump method should be used when administering a reduced dose of Pluvicto following a dose modification for an adverse reaction. When using the gravity method for a reduced dose, the Pluvicto dose should be adjusted before the administration to avoid the delivery of an incorrect volume of Pluvicto.

Prior to administration, the intravenous catheter used exclusively for Pluvicto administration should be flushed with ≥10 mL of sterile sodium chloride 9 mg/mL (0.9%) solution for injection to ensure patency and to minimise the risk of extravasation. Cases of extravasation should be managed as per institutional guidelines. Patients should be advised to remain well hydrated and to urinate frequently before and after administration of Pluvicto (see section 4.4).

For instructions on the method of preparation and intravenous methods of administration, see section 12.

For patient preparation, see section 4.4.

Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

Summary of safety profile

Unless otherwise stated, the frequency of listed adverse reactions is based on data from the VISION study in which 529 patients received at least one dose of 7 400 MBq (median number of doses was five).

The most common adverse reactions include: fatigue (48.0%), dry mouth (39.3%), nausea (35.7%), anaemia (31.9%), decreased appetite (21.4%) and constipation (20.2%). The most common grade 3 to 4 adverse reactions include: anaemia (12.9%), thrombocytopenia (7.9%), lymphopenia (7.8%) and fatigue (6.6%).

At the time of VISION final analysis, after a median follow-up duration of 14.2 months (range: 0.6 to 60.9 months), the overall safety profile remained consistent with that previously reported.

Tabulated list of adverse reactions

Adverse reactions (Table 2) are listed by MedDRA system organ class. Within each system organ class, the adverse reactions are ranked by frequency, with the most frequent reactions first. In addition, the corresponding frequency category for each adverse reaction is based on the following convention (CIOMS III): very common (≥1/10); common (≥1/100 to <1/10); uncommon (≥1/1 000 to <1/100);
rare (≥1/10 000 to <1/1 000); very rare (<1/10 000).

Table 2
Adverse reactions occurring at a higher incidence in patients who received Pluvicto plus BSoC compared to BSoC alone in VISIONa

System organ class
Adverse reaction
Frequency category
All grades n (%)
Grades
3 to 4b n (%)
Infections and infestations
Oral fungal infectionc
Common
13 (2.5)
0 (0.0)
Blood and lymphatic system disorders
Anaemia
Very common
169 (31.9)
68 (12.9)
Thrombocytopenia
Very common
91 (17.2)
42 (7.9)
Leukopeniad
Very common
83 (15.7)
22 (4.2)
Lymphopenia
Very common
75 (14.2)
41 (7.8)
Pancytopeniae
Common
9 (1.7)
7 (1.3)b
Bone marrow failure
Uncommon
1 (0.2)
1 (0.2)b
Nervous system disorders
Dizziness
Common
44 (8.3)
5 (0.9)
Headache
Common
37 (7.0)
4 (0.8)
Dysgeusiaf
Common
37 (7.0)
0 (0.0)
Eye disorders
Dry eye
Common
16 (3.0)
0 (0.0)
Ear and labyrinth disorders
Vertigo
Common
11 (2.1)
0 (0.0)
Gastrointestinal disorders
Dry mouthg
Very common
208 (39.3)
0 (0.0)
Nausea
Very common
189 (35.7)
7 (1.3)
Constipation
Very common
107 (20.2)
6 (1.1)
Vomitingh
Very common
101 (19.1)
5 (0.9)
Diarrhoea
Very common
101 (19.1)
4 (0.8)
Abdominal paini
Very common
61 (11.5)
7 (1.3)
Oesophageal disorderj
Common
18 (3.4)
1 (0.2)
Stomatitis
Common
9 (1.7)
1 (0.2)
Skin and subcutaneous tissue disorders
Dry skink
Common
8 (1.5)
0 (0.0)
Renal and urinary disorders
Urinary tract infectionl
Very common
63 (11.9)
20 (3.8)
Acute kidney injurym
Common
48 (9.1)
18 (3.4)

General disorders and administration site conditions
Fatiguen
Very common
254 (48.0)
35 (6.6)
Decreased appetite
Very common
113 (21.4)
10 (1.9)
Weight decreased
Very common
58 (11.0)
2 (0.4)
Oedema peripheralo
Very common
53 (10.0)
2 (0.4)
Pyrexia
Common
37 (7.0)
2 (0.4)
Abbreviation: BSoC, best standard of care.
a
National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 5.0.
b
Only includes grades 3 to 4 adverse reactions, with the exception of pancytopenia and bone marrow failure. Grade 5 (fatal) pancytopenia was reported in 2 patients who received Pluvicto plus BSoC. Grade 5 (fatal) bone marrow failure was reported in 1 patient who received Pluvicto plus BSoC.
c
Oral fungal infection includes oral candidiasis, candida infection, oral fungal infection, oropharyngitis fungal and tongue fungal infection.
d
Leukopenia includes leukopenia and neutropenia.
e
Pancytopenia includes pancytopenia and bicytopenia.
f
Dysgeusia includes dysgeusia and taste disorder.
g
Dry mouth includes dry mouth, lip dry, salivary hyposecretion and dry throat.
h
Vomiting includes vomiting and retching.
i
Abdominal pain includes abdominal pain, abdominal pain upper, abdominal discomfort, abdominal pain lower, abdominal tenderness and gastrointestinal pain.
j
Oesophageal disorder includes gastrooesophageal reflux disease, dysphagia and oesophagitis.
k
Dry skin includes dry skin and xeroderma.
l
Urinary tract infection includes urinary tract infection, cystitis and cystitis bacterial.
m Acute kidney injury includes blood creatinine increased, acute kidney injury, renal failure and blood urea increased.
n
Fatigue includes fatigue and asthenia.
o
Oedema peripheral includes oedema peripheral, fluid retention and hypervolaemia.

Description of selected adverse reactions

Myelosuppression
In the VISION study, myelosuppression occurred more frequently in patients who received Pluvicto plus BSoC compared to patients who received BSoC alone (all grades/grade ≥3): anaemia (31.9%/12.9%) versus (13.2%/4.9%); thrombocytopenia (17.2%/7.9%) versus (4.4%/1.0%);
leukopenia (12.5%/2.5%) versus (2.0%/0.5%); lymphopenia (14.2%/7.8%) versus (3.9%/0.5%);
neutropenia (8.5%/3.4%) versus (1.5%/0.5%); pancytopenia (1.5%/1.1%) versus (0%/0%) including two fatal events of pancytopenia in patients who received Pluvicto plus BSoC; bicytopenia (0.2%/0.2%) versus (0%/0%); and bone marrow failure (0.2%/0.2%) versus (0%/0%) including one fatal event of bone marrow failure in a patient who received Pluvicto plus BSoC.

Myelosuppression adverse reactions that led to permanent discontinuation in ≥0.5% of patients who received Pluvicto plus BSoC included: anaemia (2.8%), thrombocytopenia (2.8%), leukopenia (1.3%), neutropenia (0.8%) and pancytopenia (0.6%). Myelosuppression adverse reactions that led to dose interruptions/dose reductions in ≥0.5% of patients who received Pluvicto plus BSoC included:
anaemia (5.1%/1.3%), thrombocytopenia (3.6%/1.9%), leukopenia (1.5%/0.6%) and neutropenia (0.8%/0.6%).

Renal toxicity
In the VISION study, renal toxicity occurred more frequently in patients who received Pluvicto plus BSoC compared to patients who received BSoC alone (all grades/grades 3 to 4): blood creatinine increased (5.7%/0.2%) versus (2.4%/0.5%); acute kidney injury (3.8%/3.2%) versus (3.9%/2.4%);
renal failure (0.2%/0%) versus (0%/0%); and blood urea increased (0.2%/0%) versus (0%/0%).

Renal adverse reactions that led to permanent discontinuation in ≥0.2% of patients who received Pluvicto plus BSoC included: blood creatinine increased (0.2%). Renal adverse reactions that led to dose interruptions/dose reductions in ≥0.2% of patients who received Pluvicto plus BSoC included:
blood creatinine increased (0.2%/0.4%) and acute kidney injury (0.2%/0%).

Second primary malignancies
Exposure to ionising radiation is linked with cancer induction and a potential for development of hereditary defects. The radiation dose resulting from therapeutic exposure may result in higher incidence of cancer and mutations. In all cases it is necessary to ensure that the risks of the radiation are less than from the disease itself. As Pluvicto contributes to a patient’s overall long-term radiation exposure, which is associated with an increased risk for cancer (see section 4.4), a potential risk of second primary malignancies cannot be ruled out for radiopharmaceuticals such as Pluvicto. At the time of the VISION primary analysis (cut-off date 27-Jan-2021), cases of squamous cell carcinoma (4 patients; 0.8%) and basal cell carcinoma, malignant melanoma and squamous cell carcinoma of the skin (1 patient each; 0.2% each) were reported in patients who received Pluvicto plus BSoC.

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the national reporting system listed in Appendix V.

Individual benefit/risk justification

For each patient, the radiation exposure must be justifiable by the likely benefit. The activity administered should in every case be as low as reasonably achievable to obtain the required therapeutic effect.

Risk from radiation exposure

Pluvicto contributes to a patient’s overall long-term cumulative radiation exposure. Long-term cumulative radiation exposure is associated with an increased risk for cancer.

Radiation exposure to patients, medical personnel, and others should be minimised during and after treatment with Pluvicto consistent with institutional good radiation safety practices, patient management procedures, and instructions to the patient for follow-up radiation protection at home.

Patient preparation
Patients should be encouraged to increase oral fluids and urged to void as often as possible to reduce bladder radiation, especially after high activities, e.g. for radionuclide therapy.

After the procedure
Before the patient is released, the nuclear medicine physician or healthcare professional should explain the necessary radioprotection precautions that the patient should follow to minimise radiation exposure to others.

After each administration of Pluvicto, the following general recommendations for patients can be considered along with national, local and institutional procedures and regulations.
- Limit close contact (less than 1 metre) with others for 2 days or with children and pregnant women for 7 days.
- Refrain from sexual activity for 7 days.
- Sleep in a separate room from others for 3 days, from children for 7 days, or from pregnant women for 15 days.

Myelosuppression

In the VISION study, myelosuppression, including fatal cases, occurred more frequently in patients who received Pluvicto plus best standard of care (BSoC) compared to patients who received BSoC alone (see section 4.8).

Haematology laboratory tests, including haemoglobin, white blood cell count, absolute neutrophil count and platelet count, should be performed before and during treatment with Pluvicto. Pluvicto should be withheld, dose reduced or permanently discontinued and patients should be clinically managed as deemed appropriate based on the severity of myelosuppression (see section 4.2).

Renal toxicity

In the VISION study, renal toxicity occurred more frequently in patients who received Pluvicto plus BSoC compared to patients who received BSoC alone (see section 4.8).

Before and after administration of Pluvicto, patients should be encouraged to increase oral fluids and urged to void as often as possible, especially after high activities, e.g. for radionuclide therapy. Kidney function laboratory tests, including serum creatinine and calculated CLcr, should be performed before

and during treatment with Pluvicto. Pluvicto should be withheld, dose reduced or permanently discontinued based on the severity of renal toxicity (see section 4.2).

Renal/Hepatic impairment

Careful consideration of the benefit risk ratio in these patients is required since an increased radiation exposure is possible.

Exposure (AUC) of lutetium (177Lu) vipivotide tetraxetan is expected to increase with the degree of renal impairment (see section 5.2). Patients with mild or moderate renal impairment may be at greater risk of toxicity. Renal function and adverse reactions should be frequently monitored in patients with mild to moderate renal impairment (see section 4.2). Treatment with Pluvicto is not recommended in patients with moderate to severe renal impairment with baseline CLcr <50 mL/min or end-stage renal disease.

Fertility

Radiations of lutetium (177Lu) vipivotide tetraxetan may potentially have toxic effects on male gonads and spermatogenesis. The recommended cumulative dose of 44 400 MBq of Pluvicto results in a radiation absorbed dose to the testes within the range where Pluvicto may cause infertility. Genetic consultation is recommended if the patient wishes to have children after treatment. Cryopreservation of sperm can be discussed as an option for male patients before treatment (see section 4.6).

Contraception in males

Male patients are advised not to father a child and to use a condom for intercourse during treatment with Pluvicto and for 14 weeks after the last dose (see section 4.6).

Specific warnings

Sodium content
This medicinal product contains up to 3.9 mmol (88.75 mg) sodium per vial, equivalent to 4.4% of the WHO recommended maximum daily intake of 2 g sodium for an adult.

Precautions with respect to environmental hazard see section 6.6.

No clinical drug interaction studies were performed.

Contraception in males

Because of potential effects on spermatogenesis associated with radiations of lutetium (177Lu) vipivotide tetraxetan, male patients are advised not to father a child and to use a condom for intercourse during treatment with Pluvicto and for 14 weeks after the last dose (see section 4.4).

Pregnancy

Pluvicto is not indicated for use in females. No animal studies using lutetium (177Lu) vipivotide tetraxetan have been conducted to evaluate its effect on female reproduction and embryo-foetal development. However, all radioactive emissions, including those from Pluvicto, can cause foetal harm when administered to a pregnant woman.

Breast-feeding

Pluvicto is not indicated for use in females. There are no data on the presence of lutetium (177Lu) vipivotide tetraxetan in human milk or its effects on the breast-fed newborn/infant or on milk production.

Fertility

No studies were conducted to determine the effects of lutetium (177Lu) vipivotide tetraxetan on fertility. Radiations of lutetium (177Lu) vipivotide tetraxetan may potentially have toxic effects on male gonads and spermatogenesis. The recommended cumulative dose of 44 400 MBq of Pluvicto results in a radiation absorbed dose to the testes within the range where Pluvicto may cause infertility. Genetic consultation is recommended if the patient wishes to have children after treatment. Cryopreservation of sperm can be discussed as an option for male patients before treatment (see section 4.4).

Pluvicto may have a minor influence on the ability to drive and use machines.

In the event of administration of a radiation overdose with Pluvicto, the absorbed dose to the patient should be reduced where possible by increasing the elimination of the radionuclide from the body by frequent micturition or by forced diuresis and frequent bladder voiding. It might be helpful to estimate the effective dose that was applied.

5.
PHARMACOLOGICAL PROPERTIES

Pharmacotherapeutic group: Therapeutic radiopharmaceuticals, Other therapeutic radiopharmaceuticals, ATC code: V10XX05

Mechanism of action

The active moiety of Pluvicto is the radionuclide lutetium-177 which is linked to a small-molecule ligand that targets and binds with high affinity to PSMA, a transmembrane protein that is highly expressed in prostate cancer, including mCRPC. Upon the binding of Pluvicto to PSMA-expressing cancer cells, the beta-minus emission from lutetium-177 delivers therapeutic radiation to the targeted cell, as well as to surrounding cells, and induces DNA damage which can lead to cell death.

Pharmacodynamic effects

Vipivotide tetraxetan does not have any pharmacodynamic activity.

Clinical efficacy and safety

VISION
The efficacy of Pluvicto in patients with progressive, PSMA-positive mCRPC was evaluated in VISION, a randomised, multicentre, open-label phase III study. Eight hundred and thirty-one (N=831) adult patients were randomised (2:1) to receive either Pluvicto 7 400 MBq every 6 weeks for up to a total of 6 doses plus best standard of care (BSoC) (N=551) or BSoC alone (N=280). Patients who received 4 doses of Pluvicto were reassessed for evidence of response, signs of residual disease, and tolerability and could receive up to 2 additional doses per physician’s discretion.

To maintain castration status, all patients continued to receive a GnRH analogue or had prior bilateral orchiectomy. Eligible patients were required to have progressive, PSMA-positive mCRPC, Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 to 2, at least one metastatic lesion present on computed tomography (CT), magnetic resonance imaging (MRI) or bone scan imaging, and adequate renal, hepatic and haematological function.

Eligible patients were also required to have received at least one AR pathway inhibitor, such as abiraterone acetate or enzalutamide, and 1 or 2 prior taxane-based chemotherapy regimens (with a regimen defined as a minimum exposure of 2 cycles of a taxane). Patients treated with only 1 prior taxane-based chemotherapy regimen were eligible if the patient was unwilling or the physician deemed the patient unsuitable to receive a second regimen. Patients with unstable symptomatic central nervous system metastases or symptomatic or clinically/radiologically impending spinal cord compression were not eligible for the study. Patients underwent a gallium (68Ga) gozetotide positron emission tomography (PET) scan to evaluate PSMA expression in lesions defined by central read criteria. Eligible patients were required to have PSMA-positive mCRPC defined as having at least one tumour lesion with gallium (68Ga) gozetotide uptake greater than in normal liver. Patients were excluded if any lesions exceeding size criteria in short axis (organs ≥1 cm, lymph nodes ≥2.5 cm, bones [soft-tissue component] ≥1 cm) had uptake less than or equal to uptake in normal liver.

The pharmacokinetics of lutetium (177Lu) vipivotide tetraxetan have been characterised in 30 patients in the phase III VISION sub-study.

Absorption

Pluvicto is administered intravenously and is immediately and completely bioavailable.

The geometric mean blood exposure (area under the curve [AUCinf]) for lutetium (177Lu) vipivotide tetraxetan at the recommended dose is 52.3 ng.h/mL (geometric mean coefficient of variation [CV] 31.4%). The geometric mean maximum blood concentration (Cmax) for lutetium (177Lu) vipivotide tetraxetan at the recommended dose is 6.58 ng/mL (CV 43.5%).

Event-free probability (%)
Censoring times
(a) Lu-PSMA-617+BSoC
(b) BSoC only
No. patients still at risk
Time from randomisation (months)

Distribution

The geometric mean volume of distribution (Vz) for lutetium (177Lu) vipivotide tetraxetan is 123 L (CV 78.1%).

Vipivotide tetraxetan and non-radioactive lutetium (175Lu) vipivotide tetraxetan are each 60% to 70% bound to human plasma proteins.

Organ uptake

The biodistribution of lutetium (177Lu) vipivotide tetraxetan shows primary uptake in lacrimal glands, salivary glands, kidneys, urinary bladder wall, liver, small intestine and large intestine (left and right colon).

Elimination

The geometric mean clearance (CL) for lutetium (177Lu) vipivotide tetraxetan is 2.04 L/h (CV 31.5%).

Lutetium (177Lu) vipivotide tetraxetan is primarily eliminated renally.

Half-life

Pluvicto shows a bi-exponential elimination with a geometric mean terminal elimination half-life (t½) of 41.6 hours (CV 68.8%).

Biotransformation

Lutetium (177Lu) vipivotide tetraxetan does not undergo hepatic or renal metabolism.

In vitro evaluation of drug interaction potential

CYP450 enzymes
Vipivotide tetraxetan is not a substrate of cytochrome P450 (CYP450) enzymes. It does not induce cytochrome P450 (CYP) 1A2, 2B6 or 3A4, and it does not inhibit cytochrome P450 (CYP) 1A2, 2B6, 2C8, 2C9, 2C19, 2D6 or 3A4/5 in vitro.

Transporters