Piflufolastat F 18
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Parth Vikram Singh, MBBS[2]
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Overview
Piflufolastat F 18 is an radioactive diagnostic agent that is FDA approved for the treatment of prostate-specific membrane antigen (PSMA) positive lesions in men with prostate cancer:
- with suspected metastasis who are candidates for initial definitive therapy.
- with suspected recurrence based on elevated serum prostate-specific antigen (PSA) level.. Common adverse reactions include headache, dysgeusia, and fatigue..
Adult Indications and Dosage
FDA-Labeled Indications and Dosage (Adult)
PYLARIFY is indicated for positron emission tomography (PET) of prostate-specific membrane antigen (PSMA) positive lesions in men with prostate cancer:
- with suspected metastasis who are candidates for initial definitive therapy.
- with suspected recurrence based on elevated serum prostate-specific antigen (PSA) level.
Radiation Safety – Drug Handling
- PYLARIFY is a radioactive drug. Only authorized persons qualified by training and experience should receive, use, and administer PYLARIFY. Handle PYLARIFY with appropriate safety measures to minimize radiation exposure during administration.
- Use waterproof gloves and effective radiation shielding, including syringe shields, when preparing and handling PYLARIFY.
Recommended Dosage and Administration Instructions
Recommended Dose
- The recommended amount of radioactivity to be administered for PET imaging is 333 MBq (9 mCi) with an acceptable range of 296 MBq to 370 MBq (8 mCi to 10 mCi) administered as a single bolus intravenous injection.
Preparation and Administration
- Use aseptic technique and radiation shielding when preparing and administering PYLARIFY.
- Visually inspect the radiopharmaceutical solution. Do not use if it contains particulate matter or if it is discolored (PYLARIFY is a clear, colorless solution).
- Calculate the necessary volume to administer based on calibration time and required dose. PYLARIFY may be diluted with 0.9% Sodium Chloride Injection, USP.
- Assay the dose in a suitable dose calibrator prior to administration.
Post Administration Instructions
- Follow the PYLARIFY injection with an intravenous flush of 0.9% Sodium Chloride Injection USP.
- Dispose of any unused PYLARIFY in compliance with applicable regulations.
Patient Preparation
- Instruct patients to drink water to ensure adequate hydration prior to administration of PYLARIFY and to continue drinking and voiding frequently for the first few hours following administration to reduce radiation exposure.
Image Acquisition
The recommended start time for image acquisition is 60 minutes after PYLARIFY injection. Starting image acquisition more than 90 minutes after injection may adversely impact imaging performance. Patients should void immediately prior to image acquisition. Position the patient supine with arms above the head. Image acquisition should start from mid-thigh and proceed to the skull vertex. Scan duration is 12 minutes to 40 minutes depending on the number of bed positions (typically 6 to 8) and acquisition time per bed position (typically 2 minutes to 5 minutes).
Image Display and Interpretation
PYLARIFY binds to prostate-specific membrane antigen (PSMA). Based on the intensity of the signals, PET images obtained using PYLARIFY indicate the presence of PSMA in tissues. Lesions should be considered suspicious if uptake is greater than physiologic uptake in that tissue or greater than adjacent background if no physiologic uptake is expected. Tumors that do not express PSMA will not be visualized. Increased uptake in tumors is not specific for prostate cancer.
Radiation Dosimetry
Radiation absorbed dose estimates are shown in Table 1 for organs and tissues of adult male patients from intravenous administration of PYLARIFY. The radiation effective dose resulting from administration of 370 MBq (10 mCi) of PYLARIFY to an adult weighing 70 kg is estimated to be 4.3 mSv. The radiation doses for this administered dose to the critical organs, which are the kidneys, liver, and spleen, are 45.5 mGy, 13.7 mGy, and 10 mGy respectively. When PET/CT is performed, exposure to radiation will increase by an amount dependent on the settings used in the CT acquisition.
- Injection: clear, colorless solution in a multiple-dose vial containing 37 MBq/mL to 2,960 MBq/mL (1 mCi/mL to 80 mCi/mL) of piflufolastat F 18 at calibration date and time.
Off-Label Use and Dosage (Adult)
Guideline-Supported Use
There is limited information regarding Off-Label Guideline-Supported Use of Piflufolastat F 18 in adult patients.
Non–Guideline-Supported Use
There is limited information regarding Off-Label Non–Guideline-Supported Use of Piflufolastat F 18 in adult patients.
Pediatric Indications and Dosage
FDA-Labeled Indications and Dosage (Pediatric)
There is limited information regarding Piflufolastat F 18 FDA-Labeled Indications and Dosage (Pediatric) in the drug label.
Off-Label Use and Dosage (Pediatric)
Guideline-Supported Use
There is limited information regarding Off-Label Guideline-Supported Use of Piflufolastat F 18 in pediatric patients.
Non–Guideline-Supported Use
There is limited information regarding Off-Label Non–Guideline-Supported Use of Piflufolastat F 18 in pediatric patients.
Contraindications
None.
Warnings
Risk of Image Misinterpretation
- Imaging interpretation errors can occur with PYLARIFY imaging. A negative image does not rule out the presence of prostate cancer and a positive image does not confirm the presence of prostate cancer. The performance of PYLARIFY for imaging of patients with biochemical evidence of recurrence of prostate cancer seems to be affected by serum PSA levels.The performance of *PYLARIFY for imaging of metastatic pelvic lymph nodes prior to initial definitive therapy seems to be affected by risk factors such as Gleason score and tumor stage .
- PYLARIFY uptake is not specific for prostate cancer and may occur with other types of cancer as well as non-malignant processes and in normal tissues. Clinical correlation, which may include histopathological evaluation of the suspected prostate cancer site, is recommended.
Hypersensitivity Reactions
- Monitor patients for hypersensitivity reactions, particularly patients with a history of allergy to other drugs and foods. Reactions may not be immediate. Always have trained staff and resuscitation equipment available.
Radiation Risks
- Diagnostic radiopharmaceuticals, including PYLARIFY, expose patients to radiation. Radiation exposure is associated with a dose-dependent increased risk of cancer.
- Ensure safe handling and preparation procedures to protect patients and health care workers from unintentional radiation exposure.
- Advise patients to hydrate before and after administration and to void frequently after administration .
Adverse Reactions
Clinical Trials Experience
- Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.
- The safety of PYLARIFY was evaluated in 593 patients, each receiving one dose of PYLARIFY. The average injected activity was 340 ± 26 MBq (9.2 ± 0.7 mCi).
- The adverse reactions reported in >0.5% of patients within the studies are shown in Table 2. In addition, a hypersensitivity reaction was reported in one patient (0.2%) with a history of allergic reaction.
Postmarketing Experience
There is limited information regarding Piflufolastat F 18 Postmarketing Experience in the drug label.
Drug Interactions
Androgen deprivation therapy and other therapies targeting the androgen pathway
Androgen deprivation therapy (ADT) and other therapies targeting the androgen pathway, such as androgen receptor antagonists, may result in changes in uptake of PYLARIFY in prostate cancer. The effect of these therapies on performance of PYLARIFY PET has not been established.
Use in Specific Populations
Pregnancy
Risk Summary
- PYLARIFY is not indicated for use in females. There is no information on the risk of adverse developmental outcomes in pregnant women or animals with the use of piflufolastat F 18. All radiopharmaceuticals, including PYLARIFY, have the potential to cause fetal harm depending on the fetal stage of development and the magnitude of the radiation dose.
Pregnancy Category (AUS):
There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Piflufolastat F 18 in women who are pregnant.
Labor and Delivery
There is no FDA guidance on use of Piflufolastat F 18 during labor and delivery.
Nursing Mothers
Risk Summary
PYLARIFY is not indicated for use in females. There is no information on the presence of piflufolastat F 18 in human milk, the effect on the breastfed infant, or the effect on milk production.
Pediatric Use
The safety and effectiveness of PYLARIFY in pediatric patients have not been established.
Geriatic Use
Of the 593 patients in completed clinical studies of PYLARIFY, 355 (60%) were ≥65 years old, while 76 (12.8%) were ≥75 years old. The efficacy and safety of PYLARIFY appear similar in adult and geriatric patients with prostate cancer, although the number of patients in the trials was not large enough to allow definitive comparison.
Gender
There is no FDA guidance on the use of Piflufolastat F 18 with respect to specific gender populations.
Race
There is no FDA guidance on the use of Piflufolastat F 18 with respect to specific racial populations.
Renal Impairment
There is no FDA guidance on the use of Piflufolastat F 18 in patients with renal impairment.
Hepatic Impairment
There is no FDA guidance on the use of Piflufolastat F 18 in patients with hepatic impairment.
Females of Reproductive Potential and Males
There is no FDA guidance on the use of Piflufolastat F 18 in women of reproductive potentials and males.
Immunocompromised Patients
There is no FDA guidance one the use of Piflufolastat F 18 in patients who are immunocompromised.
Administration and Monitoring
Administration
There is limited information regarding Piflufolastat F 18 Administration in the drug label.
Monitoring
There is limited information regarding Piflufolastat F 18 Monitoring in the drug label.
IV Compatibility
There is limited information regarding the compatibility of Piflufolastat F 18 and IV administrations.
Overdosage
- In the event of an overdose of PYLARIFY, reduce the radiation absorbed dose to the patient where possible by increasing the elimination of the drug from the body using hydration and frequent bladder voiding.
- A diuretic might also be considered. If possible, an estimate of the radiation effective dose administered to the patient should be made.
Pharmacology
There is limited information regarding Piflufolastat F 18 Pharmacology in the drug label.
Mechanism of Action
- Piflufolastat F 18 binds to cells that express PSMA, including malignant prostate cancer cells, which usually overexpress PSMA.
- Fluorine-18 (F 18) is a β+ emitting radionuclide that enables positron emission tomography.
Structure
Chemical Characteristics
PYLARIFY contains fluorine 18 (F 18), radiolabeled prostate-specific membrane antigen inhibitor imaging agent. Chemically piflufolastat F 18 is 2- ( 3- { 1-carboxy-5- [ ( 6- [ 18F ] fluoro-pyridine-3-carbonyl ) –amino ] –pentyl } ureido ) -pentanedioic acid. The molecular weight is 441.4 and the structural formula is:
The chiral purity of the unlabeled piflufolastat F 18 precursor is greater than 99% ( S,S ) . PYLARIFY is a sterile, non-pyrogenic, clear, colorless solution for intravenous injection. Each milliliter contains 37 to 2,960 MBq ( 1 to 80 mCi ) piflufolastat F 18 with ≤0.01 µg/mCi of piflufolastat at calibration time and date, and ≤ 78.9 mg ethanol in 0.9% sodium chloride injection USP. The pH of the solution is 4.5 to 7.0. PYLARIFY has a radiochemical purity of at least 95% up to 10 hours following end of synthesis, and specific activity of at least 1000 mCi/µmol at the time of administration.
Physical Characteristics
PYLARIFY is radiolabeled with fluorine 18 (F 18), a cyclotron produced radionuclide that decays by positron emission to stable oxygen 18 with a half-life of 109.8 minutes. The principal photons useful for diagnostic imaging are the coincident pair of 511 keV gamma photons, resulting from the interaction of the emitted positron with an electron (Table 3).
External Radiation
The point source air-kerma coefficient for F 18 is 3.75 × 10 -17Gy m 2/(Bq s). The first half-value thickness of lead (Pb) for F 18 gamma rays is approximately 6 mm. The relative reduction of radiation emitted by F 18 that results from various thicknesses of lead shielding is shown in Table 4. The use of 8 cm Pb decreases the radiation transmission (i.e. exposure) by a factor of about 10,000.
Pharmacodynamics
The relationship between piflufolastat F 18 plasma concentrations and image interpretation has not been studied.
Pharmacokinetics
Distribution
- Following intravenous administration of piflufolastat F 18, blood levels decline in a biphasic fashion. The distribution half-life is 0.17 ± 0.044 hours and the elimination half-life is 3.47 ± 0.49 hours.
- Piflufolastat F 18 distributes to the kidneys (16.5% of administered activity), liver (9.3%), and lung (2.9%), within 60 minutes of intravenous administration.
Elimination
- Elimination is by urinary excretion. In the first 8 hours post-injection, approximately 50% of administered radioactivity is excreted in the urine.
Nonclinical Toxicology
Carcinogenesis, Mutagenesis, Impairment of Fertility
- Animal studies to assess the carcinogenicity or mutagenic potential of piflufolastat have not been conducted. However, piflufolastat has the potential to be mutagenic because of the F 18 radioisotope.
- No animal studies with piflufolastat have been performed to evaluate the potential impairment of fertility in males or females.
Clinical Studies
There is limited information regarding Piflufolastat F 18 Clinical Studies in the drug label.
How Supplied
There is limited information regarding Piflufolastat F 18 How Supplied in the drug label.
Storage
There is limited information regarding Piflufolastat F 18 Storage in the drug label.
Images
Drug Images
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Package and Label Display Panel
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Patient Counseling Information
There is limited information regarding Piflufolastat F 18 Patient Counseling Information in the drug label.
Precautions with Alcohol
Alcohol-Piflufolastat F 18 interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.
Brand Names
PYLARIFY
Look-Alike Drug Names
There is limited information regarding Piflufolastat F 18 Look-Alike Drug Names in the drug label.
Drug Shortage Status
Price
References
The contents of this FDA label are provided by the National Library of Medicine.