ADVERSE REACTIONS SECTION.

6 ADVERSE REACTIONS. The most common reported adverse reactions are headache, dysgeusia, and fatigue. (6.1)To report SUSPECTED ADVERSE REACTIONS, contact Progenics Pharmaceuticals, Inc. at 1-800-362-2668 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience. Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of 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, hypersensitivity reaction was reported in one patient (0.2%) with history of allergic reaction.Table 2. Adverse Reactions with Frequency >0.5% in Patients Who Received PYLARIFY (n 593)Adverse Reactionn (%)Headache13 (2%)Dysgeusia10 (2%)Fatigue7 (1%).

CARCINOGENESIS & MUTAGENESIS & IMPAIRMENT OF FERTILITY SECTION.

13.1 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 18 radioisotope.No animal studies with piflufolastat have been performed to evaluate the potential impairment of fertility in males or females.

CLINICAL PHARMACOLOGY SECTION.

12 CLINICAL PHARMACOLOGY. 12.1Mechanism of Action. Piflufolastat 18 binds to cells that express PSMA, including malignant prostate cancer cells, which usually overexpress PSMA. Fluorine-18 (F 18) is + emitting radionuclide that enables positron emission tomography.. 12.2Pharmacodynamics. The relationship between piflufolastat 18 plasma concentrations and image interpretation has not been studied.. 12.3Pharmacokinetics. DistributionFollowing intravenous administration of piflufolastat 18, blood levels decline in biphasic fashion. The distribution half-life is 0.17 +- 0.044 hours and the elimination half-life is 3.47 +- 0.49 hours.Piflufolastat 18 distributes to the kidneys (16.5% of administered activity), liver (9.3%), and lung (2.9%), within 60 minutes of intravenous administration.. EliminationElimination is by urinary excretion. In the first hours post-injection, approximately 50% of administered radioactivity is excreted in the urine.

CLINICAL STUDIES SECTION.

14 CLINICAL STUDIES. The safety and efficacy of PYLARIFY were evaluated in two prospective, open-label, multi-center clinical studies in men with prostate cancer: OSPREY (NCT02981368) and CONDOR (NCT03739684).. OSPREYOSPREY enrolled cohort of 268 men with biopsy-proven prostate cancer who were considered candidates for radical prostatectomy and pelvic lymph node dissection. These patients were all considered to have high risk disease based on criteria such as Gleason score, PSA level, and tumor stage. Each patient received single PYLARIFY PET/CT from mid-thigh to skull vertex.Three central readers independently interpreted each PET scan for the presence of abnormal PYLARIFY uptake in pelvic lymph nodes in multiple subregions, including the common iliac lymph nodes. The readers were blinded to all clinical information. While readers also recorded the presence of PYLARIFY PET-positive lesions in the prostate gland and outside the pelvis, those results were not included in the primary efficacy analysis.A total of 252 patients (94%) underwent standard-of-care prostatectomy and template pelvic lymph node dissection and had sufficient histopathology data for evaluation of the pelvic lymph nodes. Surgical specimens were separated into three regions: left hemipelvis, right hemipelvis, and other. For each patient, PYLARIFY PET results and histopathology results obtained from dissected pelvic lymph nodes were compared by surgical region. PET results in locations that were not dissected were excluded from analysis.For the 252 evaluable patients, the mean age was 64 years (range 46 to 84 years), and 87% were white. The median serum PSA was 9.3 ng/mL. The total Gleason score was for 19%, for 46%, and for 34% of the patients, with the remainder of the patients having Gleason scores of or 10.Table shows PYLARIFY PET performance by reader through comparison to pelvic lymph node histopathology at the patient-level with region matching, such that at least one true positive region defines true positive patient. Approximately 24% of the evaluable patients had pelvic lymph node metastases based on histopathology (95% confidence interval: 19%, 29%).Table 5: Patient-Level, Region-Matched Performance of PYLARIFY PET for Detection of Pelvic Lymph Node Metastasis in OSPREY (n=252)Reader 1Reader 2Reader 3Abbreviations: CI confidence interval, PPV positive predictive value, NPV negative predictive valueTrue Positive231723False Positive749False Negative364337True Negative186188183Sensitivity, (95% CI)39 (27, 51)28 (17, 40)38 (26, 51)Specificity, (95% CI)96 (94, 99)98 (95, 99)95 (92, 98)PPV, (95% CI)77 (62, 92)81 (59, 93)72 (56, 87)NPV, (95% CI)84 (79, 89)81 (76, 86)83 (78, 88)In exploratory analyses, there were numerical trends towards more true positive results among patients with total Gleason score of or higher and among patients with tumor stage of T2c or higher relative to those patients with lower Gleason score or tumor stage.. CONDORCONDOR enrolled 208 patients with biochemical evidence of recurrent prostate cancer, defined by serum PSA of at least 0.2 ng/mL after radical prostatectomy (with confirmatory PSA level also at least0.2 ng/mL) or by an increase in serum PSA of at least ng/mL above the nadir after other therapies. The mean age was 68 years (range 43 to 91 years), and 90% of patients were white. The median serum PSA was 0.82 ng/mL. Prior treatment included radical prostatectomy in 85% of the patients.All enrolled patients had conventional imaging evaluation (for most patients, CT or MRI) within 60 days prior to receiving PYLARIFY PET, and this evaluation was negative or equivocal for prostate cancer. All patients received single PYLARIFY PET/CT from mid-thigh to skull vertex with optional imaging of the lower extremities.Three central readers independently evaluated each PYLARIFY PET scan for the presence and location of positive lesions. Location of each lesion was categorized in one of 19 subregions that were grouped into regions (prostate/prostate bed, pelvic lymph nodes, other lymph nodes, soft tissue, bone). The readers were blinded to all clinical information.Depending on the reader, total of 123 to 137 patients (59% to 66%) had at least one lesion that was identified as PYLARIFY PET-positive (Table 6, TP FP PET-Positive Without Reference Standard). The region most commonly observed to have PYLARIFY PET-positive finding was pelvic lymph nodes (40% to 42% of all PET-positive regions) and the least common region was soft tissue (6% to 7%).Depending on the reader, 99 to 104 patients with PYLARIFY PET-positive region had location-matched composite reference standard information available (Evaluable Set, Table 6, TP FP) that consisted of histopathology, imaging (CT, MRI, ultrasound, fluciclovine PET, choline PET, or bone scan) obtained within 60 days of the PYLARIFY PET scan, or response of serum PSA level to targeted radiotherapy. Reference standard information for PET-negative regions was not systematically collected in this study.Table shows patient-level performance results of PYLARIFY PET by reader, including location -matched positive predictive value [true positive (true positive false positive)], also known as Correct Localization Rate (CLR). For these results, patient was considered true positive if they had at least one matching location positive on both PYLARIFY PET and the composite reference standard. In addition to calculating location-matched positive predictive value in the Evaluable Set (CLR), an exploratory analysis of positive predictive value in all scanned patients (Imputed CLR) was performed in which PYLARIFY PET-positive patients who lacked reference standard information were imputed using an estimated likelihood that at least one PET-positive lesion was reference standard positive, based on patient-specific factors.Table 6: Patient-Level Performance of PYLARIFY PET in CONDOR (n=208)Reader 1Reader 2Reader 3Abbreviations: TP true positive, FP false positive, CLR location-matched positive predictive value in the Evaluable Set [TP/(TP FP)], Imputed CLR location-matched positive predictive value in all scanned patients using an imputation approach based on patient-specific factors for PET-Positive Without Reference Standard, CI confidence intervalTrue Positive (TP)898784False Positive (FP)151315PET-Positive Without Reference Standard332424PET-Negative718485CLR (95% CI)86 (79, 92)87 (80, 94)85 (78, 92)Imputed CLR (95% CI)78 (71, 85)81 (74, 88)79 (72, 86)An exploratory analysis of region-level positive predictive value using only PET-positive regions that had sufficient composite reference standard information to determine true positive or false positive status demonstrated results of 67% to 70% with the lower bound of the 95% confidence interval ranging from 59% to 63%.The percentage of patients categorized as true positive in location-matched analysis out of all patients scanned with PYLARIFY was an additional exploratory endpoint. Using the same imputation approach for PET-positive patients who lacked reference standard information as in Table above, this value was 47% to 51%, with the lower bound of the 95% confidence interval ranging from 40% to 45%.Table shows patient-level PYLARIFY PET results from the majority read stratified by serum PSA level. Percent PET positivity was calculated as the proportion of patients with positive PYLARIFY PET out of all patients scanned. Percent PET positivity includes patients determined to be either true positive or false positive as well as those in whom such determination was not made due to lack of composite reference standard information. The likelihood of patient having at least one PYLARIFY PET-positive lesion generally increased with higher serum PSA level.Table 7: Patient-Level PYLARIFY PET Results and Percent PET PositivityPercent PET positivity PET positive patients/total patients scanned. PET positive patients include true positive and false positive patients as well as those who did not have reference standard information. Stratified by Serum PSA Level in the CONDOR Study Using Majority Result Among Three Readers (n=199)Six patients were excluded from this table due to lack of baseline PSA level. Three patients were excluded from this table due to lack of majority result among the categories true positive, false positive, PET positive without reference standard, and PET negative. PSA (ng/mL)PET positive patientsPET negative patientsPercent PET positivity, (95% CI)TotalTPFPWithout reference standardWith reference standardAbbreviations: TP true positive, FP false positive, CI confidence interval<0.52411494535 (24, 46)15>=0.5 and <11812331850 (34, 66)15>=1 and <22115331068 (51, 84)18>=2575034690 (83, 98)53Total1208813197960 (54, 67)101.

CLINICAL TRIALS EXPERIENCE SECTION.

6.1 Clinical Trials Experience. Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of 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, hypersensitivity reaction was reported in one patient (0.2%) with history of allergic reaction.Table 2. Adverse Reactions with Frequency >0.5% in Patients Who Received PYLARIFY (n 593)Adverse Reactionn (%)Headache13 (2%)Dysgeusia10 (2%)Fatigue7 (1%).

CONTRAINDICATIONS SECTION.

4 CONTRAINDICATIONS. None.. None. (4).

DESCRIPTION SECTION.

11 DESCRIPTION. 11.1 Chemical Characteristics. PYLARIFY contains fluorine 18 (F 18), radiolabeled prostate-specific membrane antigen inhibitor imaging agent. Chemically piflufolastat 18 is 2-(3-1-carboxy-5-[(6-[18F]fluoro-pyridine-3-carbonyl)-amino]-pentylureido)-pentanedioic acid. The molecular weight is 441.4 and the structural formula is:The chiral purity of the unlabeled piflufolastat 18 precursor is greater than 99% (S,S).PYLARIFY is sterile, non-pyrogenic, clear, colorless solution for intravenous injection. Each milliliter contains 37 to 2,960 MBq (1 to 80 mCi) piflufolastat 18 with <=0.01 ug/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 radiochemical purity of at least 95% up to 10 hours following end of synthesis, and specific activity of at least 1000 mCi/umol at the time of administration.. Chemical Structure. 11.2 Physical Characteristics. PYLARIFY is radiolabeled with fluorine 18 (F 18), cyclotron produced radionuclide that decays by positron emission to stable oxygen 18 with 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).Table 3. Principal Radiation Produced from Decay of Fluorine 18Radiation Energy (keV)Abundance (%)Positron249.896.9Gamma511193.5. 11.3 External Radiation. The point source air-kerma coefficient for 18 is 3.75 10-17 Gy m2/(Bq s). The first half-value thickness of lead (Pb) for 18 gamma rays is approximately mm. The relative reduction of radiation emitted by 18 that results from various thicknesses of lead shielding is shown in Table 4. The use of cm Pb decreases the radiation transmission (i.e. exposure) by factor of about 10,000.Table 4. Radiation Attenuation of 511 keV Gamma Rays by Lead ShieldingShield Thickness cm of Lead (Pb)Coefficient of Attenuation0.60.520.140.0160.00180.0001.

DOSAGE & ADMINISTRATION SECTION.

2 DOSAGE AND ADMINISTRATION. Recommended dose is 333 MBq (9 mCi) with an acceptable range of 296 MBq to 370 MBq (8 mCi to 10 mCi), administered as bolus intravenous injection. (2.2)Initiate imaging approximately 60 minutes after PYLARIFY administration. The patient should void immediately prior to initiation of imaging. Image acquisition should start from mid-thigh and proceed to the skull vertex. (2.3, 2.4)See full prescribing information for additional preparation, handling, administration, imaging, and radiation dosimetry information. (2). Recommended dose is 333 MBq (9 mCi) with an acceptable range of 296 MBq to 370 MBq (8 mCi to 10 mCi), administered as bolus intravenous injection. (2.2). Initiate imaging approximately 60 minutes after PYLARIFY administration. The patient should void immediately prior to initiation of imaging. Image acquisition should start from mid-thigh and proceed to the skull vertex. (2.3, 2.4). See full prescribing information for additional preparation, handling, administration, imaging, and radiation dosimetry information. (2). 2.1 Radiation Safety Drug Handling. PYLARIFY is 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 [see Warnings and Precautions (5.3)]. Use waterproof gloves and effective radiation shielding, including syringe shields, when preparing and handling PYLARIFY.. 2.2 Recommended Dosage and Administration Instructions. Recommended DoseThe 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 single bolus intravenous injection.. Preparation and AdministrationUse 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 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 suitable dose calibrator prior to 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 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 suitable dose calibrator prior to administration.. Post Administration InstructionsFollow the PYLARIFY injection with an intravenous flush of 0.9% Sodium Chloride Injection USP.Dispose of any unused PYLARIFY in compliance with applicable regulations.. 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.. 2.3 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 [see Warnings and Precautions (5.3)].. 2.4 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 to 8) and acquisition time per bed position (typically minutes to minutes).. 2.5 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 [see Warnings and Precautions (5.1) ].. 2.6 Radiation Dosimetry. Radiation absorbed dose estimates are shown in Table 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.Table 1. Estimated Radiation Absorbed Doses in Organs/Tissues in Adults who Received PYLARIFYOrgan/TissueMean Absorbed dose per Unit Administered Activity(mGy/MBq)MeanStandard DeviationAdrenal glands0.01310.0013Brain0.00210.0003Breasts0.00580.0007Gallbladder wall0.01410.0012Lower large intestine wall0.00730.001Small intestine0.00890.0009Stomach wall0.00920.0008Upper large intestine wall0.00910.0009Heart wall0.01710.0022Kidneys0.1230.0434Liver0.0370.0058Lungs0.01020.0016Muscle0.00690.0008Pancreas0.01240.0011Red bone marrow0.00710.0007Osteogenic cells0.00990.0012Skin0.00520.0006Spleen0.02710.0115Testes0.00590.0008Thymus gland0.0070.0008Thyroid0.00620.0009Urinary bladder wall0.00720.001Effective dose0.0116 (mSv/MBq)0.0022 (mSv/MBq).

DOSAGE FORMS & STRENGTHS SECTION.

3 DOSAGE FORMS AND STRENGTHS. Injection: clear, colorless solution in multiple-dose vial containing 37 MBq/mL to 2,960 MBq/mL (1 mCi/mL to 80 mCi/mL) of piflufolastat 18 at calibration date and time.. Injection: clear, colorless solution in multiple-dose vial containing 37 MBq/mL to 2,960 MBq/mL (1 mCi/mL to 80 mCi/mL) of piflufolastat 18 at calibration date and time. (3).

DRUG INTERACTIONS SECTION.

7 DRUG INTERACTIONS. Androgen deprivation therapy and other therapies targeting the androgen pathwayAndrogen 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.

GERIATRIC USE SECTION.

8.5 Geriatric 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.

HOW SUPPLIED SECTION.

16 HOW SUPPLIED/STORAGE AND HANDLING. 16.1 How Supplied. PYLARIFY injection is supplied in 50 mL multiple-dose glass vial (NDC 71258-022-01) containing clear, colorless solution at strength of 37 MBq/mL to 2,960 MBq/mL (1 mCi/mL to 80 mCi/mL) piflufolastat 18 at calibration time and date.. 16.2 Storage and Handling. StorageStore PYLARIFY at controlled room temperature (USP) 20C to 25C (68F to 77F). PYLARIFY does not contain preservative. Store PYLARIFY in the original container with radiation shielding. The expiration date and time are provided on the container label. Use PYLARIFY within 10 hours from the time of end of synthesis.. HandlingThis preparation is approved for use by persons under license by the Nuclear Regulatory Commission or the relevant regulatory authority of an Agreement State.

INDICATIONS & USAGE SECTION.

1 INDICATIONS AND USAGE. 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.. with suspected metastasis who are candidates for initial definitive therapy.. with suspected recurrence based on elevated serum prostate-specific antigen (PSA) level.. PYLARIFY is radioactive diagnostic agent 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. (1). with suspected metastasis who are candidates for initial definitive therapy.. with suspected recurrence based on elevated serum prostate-specific antigen (PSA) level. (1).

INFORMATION FOR PATIENTS SECTION.

17 PATIENT COUNSELING INFORMATION. Adequate HydrationInstruct patients to drink sufficient amount of water to ensure adequate hydration before their PET study and urge them to drink and urinate as often as possible during the first hours following the administration of PYLARIFY, in order to reduce radiation exposure [see Dosage and Administration (2.3) and Warnings and Precautions (5.3) ].

LACTATION SECTION.

8.2 Lactation. Risk SummaryPYLARIFY is not indicated for use in females. There is no information on the presence of piflufolastat 18 in human milk, the effect on the breastfed infant, or the effect on milk production.

MECHANISM OF ACTION SECTION.

12.1Mechanism of Action. Piflufolastat 18 binds to cells that express PSMA, including malignant prostate cancer cells, which usually overexpress PSMA. Fluorine-18 (F 18) is + emitting radionuclide that enables positron emission tomography.

NONCLINICAL TOXICOLOGY SECTION.

13 NONCLINICAL TOXICOLOGY. 13.1 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 18 radioisotope.No animal studies with piflufolastat have been performed to evaluate the potential impairment of fertility in males or females.

OVERDOSAGE SECTION.

10 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. diuretic might also be considered. If possible, an estimate of the radiation effective dose administered to the patient should be made.

PACKAGE LABEL.PRINCIPAL DISPLAY PANEL.

PRINCIPAL DISPLAY PANEL 50 mL Vial Label. SterilePYLARIFY(R) (piflufolastat 18) injectionNon-pyrogenic37 MBq/mL to 2,960 MBq/mL (1 mCi/mL to 80 mCi/mL) at end of synthesis (EOS)Diagnostic For Intravenous Use Only Expires 10 hours after EOSBatch EOS Date:EOS Time:Activity EOS:mCiConcentration:mCi/mLVolume:mLExp. Date:Exp. Time: NDC: 71258-022-01Each ml contains 37 MBq to 2,960 MBq (1 mCi to 80 mCi) piflufolastat 18 at EOS, and<= 78.9 mg ethanol in 0.9% sodium chloride injection, USPMultiple-Dose VialStore PYLARIFY upright in shielded container at controlled room temperature (USP) 20C to 25C (68F to 77F)Do not use if discolored or if it contains particulate matter. Calculate correct dosage from date and time of calibration. Recommended Dosage: See Prescribing InformationCAUTION: RADIOACTIVE MATERIALManufactured for: Progenics Pharmaceuticals, Inc.N. Billerica, MA 0186218F Half-life 109.8 minutes RX Only 516109-0421. PRINCIPAL DISPLAY PANEL 50 mL Vial Label.

PEDIATRIC USE SECTION.

8.4 Pediatric Use. The safety and effectiveness of PYLARIFY in pediatric patients have not been established.

PHARMACODYNAMICS SECTION.

12.2Pharmacodynamics. The relationship between piflufolastat 18 plasma concentrations and image interpretation has not been studied.

PHARMACOKINETICS SECTION.

12.3Pharmacokinetics. DistributionFollowing intravenous administration of piflufolastat 18, blood levels decline in biphasic fashion. The distribution half-life is 0.17 +- 0.044 hours and the elimination half-life is 3.47 +- 0.49 hours.Piflufolastat 18 distributes to the kidneys (16.5% of administered activity), liver (9.3%), and lung (2.9%), within 60 minutes of intravenous administration.. EliminationElimination is by urinary excretion. In the first hours post-injection, approximately 50% of administered radioactivity is excreted in the urine.

PREGNANCY SECTION.

8.1 Pregnancy. Risk SummaryPYLARIFY 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 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.

SPL UNCLASSIFIED SECTION.

2.1 Radiation Safety Drug Handling. PYLARIFY is 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 [see Warnings and Precautions (5.3)]. Use waterproof gloves and effective radiation shielding, including syringe shields, when preparing and handling PYLARIFY.

STORAGE AND HANDLING SECTION.

16.2 Storage and Handling. StorageStore PYLARIFY at controlled room temperature (USP) 20C to 25C (68F to 77F). PYLARIFY does not contain preservative. Store PYLARIFY in the original container with radiation shielding. The expiration date and time are provided on the container label. Use PYLARIFY within 10 hours from the time of end of synthesis.. HandlingThis preparation is approved for use by persons under license by the Nuclear Regulatory Commission or the relevant regulatory authority of an Agreement State.

USE IN SPECIFIC POPULATIONS SECTION.

8 USE IN SPECIFIC POPULATIONS. 8.1 Pregnancy. Risk SummaryPYLARIFY 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 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.. 8.2 Lactation. Risk SummaryPYLARIFY is not indicated for use in females. There is no information on the presence of piflufolastat 18 in human milk, the effect on the breastfed infant, or the effect on milk production.. 8.4 Pediatric Use. The safety and effectiveness of PYLARIFY in pediatric patients have not been established.. 8.5 Geriatric 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.

WARNINGS AND PRECAUTIONS SECTION.

5 WARNINGS AND PRECAUTIONS. Risk of Image Misinterpretation: PYLARIFY uptake can be seen in variety of tumor types as well as in non-malignant processes and normal tissues. Image interpretation errors can occur with PYLARIFY imaging. (5.1)Hypersensitivity Reactions: Monitor patients for hypersensitivity reactions, particularly patients with history of allergy to other drugs and foods. (5.2)Radiation Risk: Ensure safe drug handling to protect patients and health care workers from unintentional radiation exposure. (5.3). Risk of Image Misinterpretation: PYLARIFY uptake can be seen in variety of tumor types as well as in non-malignant processes and normal tissues. Image interpretation errors can occur with PYLARIFY imaging. (5.1). Hypersensitivity Reactions: Monitor patients for hypersensitivity reactions, particularly patients with history of allergy to other drugs and foods. (5.2). Radiation Risk: Ensure safe drug handling to protect patients and health care workers from unintentional radiation exposure. (5.3). 5.1 Risk of Image Misinterpretation. Imaging interpretation errors can occur with PYLARIFY imaging. negative image does not rule out the presence of prostate cancer and 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 [see Clinical Studies (14) ]. 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 [see Clinical Studies (14) ]. 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.. 5.2 Hypersensitivity Reactions. Monitor patients for hypersensitivity reactions, particularly patients with history of allergy to other drugs and foods. Reactions may not be immediate. Always have trained staff and resuscitation equipment available.. 5.3 Radiation Risks. Diagnostic radiopharmaceuticals, including PYLARIFY, expose patients to radiation [see Dosage and Administration (2.6)]. Radiation exposure is associated with 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 [see Dosage and Administration (2.3)].