HIGHLIGHTS OF PRESCRIBING INFORMATION

{ "type": "p", "children": [], "text": "\nHIGHLIGHTS OF PRESCRIBING INFORMATION\n" }

These highlights do not include all the information needed to use ASCOR® safely and effectively. See full prescribing information for ASCOR.

{ "type": "p", "children": [], "text": "These highlights do not include all the information needed to use \n ASCOR® safely and effectively. See full prescribing information for \n ASCOR.\n" }

ASCOR (ascorbic acid injection), for intravenous use Initial U.S. Approval: 1947

{ "type": "p", "children": [], "text": "\nASCOR (ascorbic acid injection), for intravenous use Initial U.S. Approval: 1947\n " }

ASCOR is vitamin C indicated for the short term (up to 1 week) treatment of scurvy in adult and pediatric patients age 5 months and older for whom oral administration is not possible, insufficient or contraindicated.

{ "type": "p", "children": [], "text": "ASCOR is vitamin C indicated for the short term (up to 1 week) treatment of scurvy in adult and pediatric patients age 5 months and older for whom oral administration is not possible, insufficient or contraindicated." }

Limitations of Use

{ "type": "p", "children": [], "text": "Limitations of Use" }

ASCOR is not indicated for treatment of vitamin C deficiency that is not associated with signs and symptoms of scurvy.

{ "type": "p", "children": [], "text": "ASCOR is not indicated for treatment of vitamin C deficiency that is not associated with signs and symptoms of scurvy." }

a. Use only in a suitable ISO Class 5 work area such as a laminar flow hood (or an equivalent clean air compounding area)

b. Penetrate each PBP vial closure only one time with a suitable sterile transfer device or dispensing set that allows measured dispensing of the contents. Given that pressure may develop within the vial during storage, excercise caution when withdrawing contents from the vial.

c. Once the closure system has been penetrated, complete all dispensing from the PBP vial within 4 hours. Each dose must be used immediately. Discard unused portion.

d. Prior to administration, ASCOR must be diluted in a suitable infusion solution and the final solution for infusion must be isotonic (undiluted the osmolarity of ASCOR is approximately 5,900 mOsmol/L). Prior to preparing the admixture for infusion, calculate the osmolarity of the intended admixture for infusion. Add one daily dose of ASCOR directly to an appropriate volume of a suitable infusion solution (e.g., 5% Dextrose Injection, Sterile Water for Injection) and add appropriate solutes, as necessary, to make final solution isotonic. Sterile Water for Injection is highly hypotonic; adjust solute content, as necessary, to make thet final infusion solution isotonic prior to injection. Do not mix ASCOR with solutions containing elemental compounds that can be reduced (e.g., copper). The concentration of ascorbic acid in the final, admixture solution for infusion is to be the range of 1 to 25 mg of ascorbic acid per mL. For example, for the largest recommended dose:

Add 200 mg of ascorbic acid (equivalent to 0.4 mL of ASCOR) to 7.5 mL of Sterile Water for Injection to produce an infusion solution having an approximate osmolarity of 290 mOsmol/L. In this specific example, addition of solute is NOT necessary because the solution is isotonic.

e. Prepare the recommended dose based on the patient population [ see Dosage and Administration (2.2), (2.3)].

f. Visually inspect for particulate matter and discoloration prior to administration (the diluted ASCOR solution should appear colorless to pale yellow).

g. Immediately administer the admixture for infusion as a slow intravenous infusion [ see Recommended Dosage, (2.2)]

Table 1 provides recommended doses of ASCOR based on patient population and infusion rates of diluted ASCOR solution.

<div class="scrollingtable"><table width="100%"> <caption> <span> Table 1: Recommended Dose of ASCOR and Infusion Rate of Diluted ASCOR Solution</span> </caption> <tbody class="Headless"> <tr class="First"> <td>Patient Population</td><td align="center">ASCOR <br/> Once Daily Dose <br/>(mg) </td><td align="center">Infusion Rate of <br/>Diluted ASCOR <br/>Solution (mg/minute) </td> </tr> <tr> <td>Pediatric Patients age 5 months to less than 12 months</td><td align="center">50</td><td align="center">1.3</td> </tr> <tr> <td>Pediatric Patients age 1 year to less than 11 years</td><td align="center">100</td><td align="center">3.3</td> </tr> <tr class="Last"> <td>Adults and Pediatric Patients 11 years and older</td><td align="center">200</td><td align="center">33</td> </tr> </tbody> </table></div>

The recommended maximum duration of daily treatment with ASCOR is seven days. If no improvement in scorbutic symptoms is observed after one week of treatment, retreat until resolution of scorbutic symptoms is observed. 

Repeat dosing is not recommended in pediatric patients less than 11 years of age.

Women who are pregnant or lactating and patients with glucose-6-dehydrogenase deficiency should not exceed the U.S. Recommended Dietary Allowance (RDA) or daily Adequate Intake (AI) level for ascorbic acid for their age group and condition [ ​ see Warnings and Precautions (5.2) and Use in Specific Populations (8.1, 8.2)].

Injection: 25,000 mg/50 mL (500 mg/mL) - Pharmacy Bulk Package

{ "type": "p", "children": [], "text": "Injection: 25,000 mg/50 mL (500 mg/mL) - Pharmacy Bulk Package" }

None.

{ "type": "p", "children": [], "text": "None. " }

Acute and chronic oxalate nephropathy have been reported with prolonged administration of high doses of ascorbic acid.  Acidification of the urine by ascorbic acid may cause precipitation of cysteine, urate or oxalate stones.  Patients with renal disease including renal impairment, history of oxalate kidney stones, and geriatric patients may be at increased risk for oxalate nephropathy while receiving treatment with ascorbic acid.  Pediatric patients less than 2 years of age may be at increased risk for oxalate nephropathy during treatment with ascorbic acid because their kidneys are immature [see Use in Specific Populations ( 8.4, 8.5, 8.6)].  Monitor renal function in patients at increased risk receiving ASCOR. Discontinue ASCOR in patients who develop oxalate nephropathy and treat any suspected oxalate nephropathy.

ASCOR is not indicated for prolonged administration (the maximum recommended duration is one week) [see Dosage and Administration ( 2.1)] .

Hemolysis has been reported with administration of ascorbic acid in patients with glucose-6-phosphate dehydrogenase deficiency. Patients with glucose-6-phosphate dehydrogenase deficiency may be at increased risk for severe hemolysis during treatment with ascorbic acid. Monitor hemoglobin and blood count and use a reduced dose of ASCOR in patients with glucose-6-phosphate dehydrogenase deficiency [see Dosage and Administration (2.3)]. Discontinue treatment with ASCOR if hemolysis is suspected and treat as needed.

Ascorbic acid may interfere with laboratory tests based on oxidation-reduction reactions, including blood and urine glucose testing, nitrite and bilirubin levels, and leucocyte count testing.  If possible, laboratory tests based on oxidation-reduction reactions should be delayed until 24 hours after infusion of ASCOR [see Drug Interactions ( 7.4)].

The following adverse reactions are discussed in greater detail in other sections of the labeling:

{ "type": "p", "children": [], "text": "The following adverse reactions are discussed in greater detail in other sections of the labeling:" }

Oxalate nephropathy and Nephrolithiasis [see Warnings and Precautions (5.1)] Hemolysis in patients with glucose-6-phosphate dehydrogenase deficiency [see Warnings and Precautions (5.2)]

{ "type": "p", "children": [], "text": " Oxalate nephropathy and Nephrolithiasis [see Warnings and Precautions (5.1)]\n \n Hemolysis in patients with glucose-6-phosphate dehydrogenase deficiency [see Warnings and Precautions (5.2)]\n " }

The following adverse reactions associated with the use of ascorbic acid were identified in the literature. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to estimate their frequency reliably or to establish a causal relationship to drug exposure:

{ "type": "p", "children": [], "text": "The following adverse reactions associated with the use of ascorbic acid were identified in the literature. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to estimate their frequency reliably or to establish a causal relationship to drug exposure:" }

Administration site reactions: pain and swelling.

{ "type": "p", "children": [], "text": "Administration site reactions: pain and swelling." }

ASCOR should not be rapidly administered. Rapid intravenous administration (>250 mg/minute) of ASCOR may cause temporary faintness or nausea, lethargy, flushing, dizziness, and headache (the recommended infusion rates of diluted ASCOR solution are 1.3 mg/minute (Pediatric Patients age 5 months to less than 12 months), 3.3 mg/minute (Pediatric Patients age 1 year to less than 11 years) and 33 mg/minute (Adults and Pediatric Patients 11 years and older) [see Dosage and Administration (2.2)]).

{ "type": "p", "children": [], "text": "ASCOR should not be rapidly administered. Rapid intravenous administration (>250 mg/minute) of ASCOR may cause temporary faintness or nausea, lethargy, flushing, dizziness, and headache (the recommended infusion rates of diluted ASCOR solution are 1.3 mg/minute (Pediatric Patients age 5 months to less than 12 months), 3.3 mg/minute (Pediatric Patients age 1 year to less than 11 years) and 33 mg/minute (Adults and Pediatric Patients 11 years and older) [see Dosage and Administration (2.2)])." }

Acute and chronic oxalate nephropathy have occurred with prolonged administration of high doses of ascorbic acid [see Warnings and Precautions (5.1)]. In patients with glucose-6-phosphate dehydrogenase deficiency severe hemolysis has occurred [see Warnings and Precautions (5.2)].

{ "type": "p", "children": [], "text": "Acute and chronic oxalate nephropathy have occurred with prolonged administration of high doses of ascorbic acid [see Warnings and Precautions (5.1)]. In patients with glucose-6-phosphate dehydrogenase deficiency severe hemolysis has occurred [see Warnings and Precautions (5.2)]." }

7.1 Antibiotics

Ascorbic acid may decrease activities of erythromycin, kanamycin, streptomycin, doxycycline, and lincomycin. Bleomycin is inactivated in vitro by ascorbic acid. If the antibiotic efficacy is suspected to be decreased by concomitant administration of ASCOR, discontinue ASCOR administration.

7.2Amphetamine & Other Drugs Affected by Urine Acidification

Ascorbic acid may acidify the urine and lower serum concentrations of amphetamine by increasing renal excretion (as reflected by changes in amphetamine urine recovery rates). In case of decreased amphetamine efficacy discontinue ASCOR administration. Standard monitoring of therapy is warranted.

In addition, acidification of urine by ascorbic acid will alter the excretion of certain drugs affected by the pH of the urine (e.g., fluphenazine) when administered concurrently. It has been reported that concurrent administration of ascorbic acid and fluphenazine has resulted in decreased fluphenazine plasma concentrations. Standard monitoring of therapy is warranted.

7.3 Warfarin

Limited case reports have suggested interference of ascorbic acid with the anticoagulation effects of warfarin, however, patients on warfarin therapy treated with ascorbic acid doses up to 1000 mg/day (5 times the largest recommended single dose) for 2 weeks (twice the maximum recommended duration), no effect was observed. Standard monitoring for anti-coagulation therapy should continue during ascorbic acid treatment, as per standard of care.

7.4 Laboratory Test Interference

Because ascorbic acid is a strong reducing agent, it can interfere with numerous laboratory tests based on oxidation-reduction reactions (e.g., glucose, nitrite and bilirubin levels, leukocyte count, etc.). Chemical detecting methods based on colorimetric reactions are generally those tests affected. Ascorbic acid may lead to inaccurate results (false negatives) obtained for checking blood or urinary glucose levels, nitrite, bilirubin, and leukocytes if tested during or within 24 hours after infusion [see Warnings and Precautions (5.3)] .

8.1 Pregnancy

Risk Summary

There are no available data on use of ASCOR in pregnant women to inform a drug-associated risk of adverse developmental outcomes; however, use of ascorbic acid (vitamin C) has been used during pregnancy for several decades and no adverse developmental outcomes are reported in the published literature [see Data]. There are dose adjustments for ascorbic acid (vitamin C) use during pregnancy [ see Clinical Considerations].

Animal reproduction studies have not been conducted with ASCOR.

The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively.

Clinical Considerations

Dose Adjustments During Pregnancy and Post-Partum Period

Follow the U.S. Recommended Dietary Allowances (RDA) for pregnant women when considering use of ASCOR for treatment of scurvy [ see Dosage and Administration (2.3)].

Data

Human Data

There are no available data on use of ASCOR or another ascorbic acid injection in pregnant women. However, a published meta–analysis of randomized studies evaluating a large number of pregnant women who took oral ascorbic acid (vitamin C) (through diet and supplementation) at doses ranging from 500 to1000 mg/day (2.5 to 5 times the recommended daily intravenous dose, respectively) [ see Dosage and Administration (2.3)] between the 9th and 16th weeks of pregnancy showed no increased risk of adverse pregnancy outcomes such as miscarriage, preterm premature rupture of membranes, preterm delivery or pregnancy induced hypertension when compared to placebo. These data cannot definitely establish or exclude the absence of a risk with ascorbic acid (vitamin C) during pregnancy.

8.2 Lactation

Risk Summary

There are no data on the presence of ascorbic acid (vitamin C) in human milk following intravenous dosing in lactating women. Ascorbic acid (vitamin C) is present in human milk after maternal oral intake. Maternal oral intake of ascorbic acid (vitamin C) exceeding the U.S. Recommended Dietary Allowances (RDA) for lactation does not influence the ascorbic acid (vitamin C) content in breast milk or the estimated daily amount received by breastfed infants. There are no data on the effect of ascorbic acid (vitamin C) on milk production or the breastfed infant. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for ASCOR and any potential adverse effects on the breastfed child from ASCOR or from the underlying maternal condition. Follow the U.S. Recommended Dietary Allowances (RDA) for lactating women when considering use of ASCOR for treatment of scurvy [see Dosage and Administration (2.3)].

8.4 Pediatric Use

ASCOR is indicated for the short term (up to 1 week) treatment of scurvy in pediatric patients age 5 months and older for whom oral administration is not possible, insufficient or contraindicated. The safety profile of ascorbic acid in pediatric patients is similar to adults; however, pediatric patients less than 2 years of age may be at higher risk of oxalate nephropathy following ascorbic acid administration due to age-related decreased glomerular filtration [ see Warnings and Precautions (5.1)].

Ascor is not indicated for use in pediatric patients less than 5 months of age.

8.5 Geriatric Use

Glomerular filtration rate is known to decrease with age and as such may increase risk for oxalate nephropathy following ascorbic acid administration in elderly population [ see Warnings and Precautions (5.1) ].

8.6 Renal Impairment

ASCOR should be used with caution in scorbutic patients with a history of or risk of developing renal oxalate stones or evidence of renal impairment or other issues (e.g., patients on dialysis, patients with diabetic nephropathy, and renal transplant recipients). These patients may be at increased risk of developing acute or chronic oxalate nephropathy following high dose ascorbic acid administration [ see Warning and Precaution (5.1].

Overdose with ascorbic acid may cause nausea, vomiting, diarrhea, facial flushing, rash, headache, fatigue or disturbed sleep. If overdose of ASCOR occurs, immediately discontinue administration and treat symptoms and signs of overdose, avoiding additional intake of ascorbic acid.

{ "type": "p", "children": [], "text": "Overdose with ascorbic acid may cause nausea, vomiting, diarrhea, facial flushing, rash, headache, fatigue or disturbed sleep. If overdose of ASCOR occurs, immediately discontinue administration and treat symptoms and signs of overdose, avoiding additional intake of ascorbic acid." }

ASCOR (ascorbic acid injection) for intravenous use is a colorless to pale yellow, preservative-free, hypertonic, sterile, non-pyrogenic solution of ascorbic acid. ASCOR must be diluted with an appropriate infusion solution (e.g., 5% Dextrose Injection, USP, Sterile Water for Injection, USP) [see Dosage and Administration (2.1)] .

{ "type": "p", "children": [], "text": "ASCOR (ascorbic acid injection) for intravenous use is a colorless to pale yellow, preservative-free, hypertonic, sterile, non-pyrogenic solution of ascorbic acid. ASCOR must be diluted with an appropriate infusion solution (e.g., 5% Dextrose Injection, USP, Sterile Water for Injection, USP) \n [see Dosage and Administration \n (2.1)] \n .\n " }

The chemical name of Ascorbic Acid is L-ascorbic acid. The molecular formula is C 6H 8O 6. It has the following structural formula:

{ "type": "p", "children": [], "text": "The chemical name of Ascorbic Acid is \n L-ascorbic acid. The molecular formula is C \n 6H \n 8O \n 6. It has the following structural formula:\n " }

Each ASCOR, 50 mL, Pharmacy Bulk Package vial contains 25,000 mg ascorbic acid, equivalent to 28,125 mg sodium ascorbate.

{ "type": "p", "children": [], "text": "Each ASCOR, 50 mL, Pharmacy Bulk Package vial contains 25,000 mg ascorbic acid, equivalent to 28,125 mg sodium ascorbate." }

Each mL of ASCOR contains 500 mg of ascorbic acid (equivalent to 562.5 mg of sodium ascorbate which amounts to 65 mg sodium/mL of ASCOR), 130 mg of Sodium bicarbonate, and 0.25mg of edetate disodium. Sodium hydroxide is added for pH adjustment (pH range 5.6-6.6). It contains no bacteriostatic or antimicrobial agent.

{ "type": "p", "children": [], "text": "Each mL of ASCOR contains 500 mg of ascorbic acid\n \n(equivalent to 562.5 mg of sodium ascorbate which amounts\n \nto 65 mg sodium/mL of ASCOR), 130 mg of Sodium\n \nbicarbonate, and 0.25mg of edetate disodium. Sodium\n \nhydroxide is added for pH adjustment (pH range 5.6-6.6).\n \nIt contains no bacteriostatic or antimicrobial agent.\n " }

The exact mechanism of action of ascorbic acid for the treatment of symptoms and signs of scurvy (a disorder caused by severe deficiency in vitamin C) is unknown; however, administration of ascorbic acid in patients with scurvy is thought to restore the body pool of ascorbic acid.

In a single pharmacokinetic study, healthy male and female adults (n=8) were given a single intravenous dose of 1000 mg ascorbic acid (5 times the largest recommended single dose) infused over a 30 minute period. The mean peak exposure to ascorbic acid was 436.2 µM and occurred at the end of the 30 minute infusion.

Distribution

Ascorbic acid is distributed widely in the body, with large concentrations found in the liver, leukocytes, platelets, glandular tissues, and lens of the eye. Based on data from oral exposure, ascorbic acid is known to be distributed into breast milk and crosses the placental barrier.

Elimination

When the body is saturated with ascorbic acid, the plasma concentration will be about the same as that of the renal threshold; if further amounts are then administered, most of it is excreted in the urine. When body tissues are not saturated and plasma concentration is low, administration of ascorbic acid results in little or no renal excretion. The mean±SD (N=3) half-life observed in the single dose PK study as described above, was 7.4±1.4 h.

Metabolism

A major route of metabolism of ascorbic acid involves its conversion to urinary oxalate, presumably through intermediate formation of its oxidized product, dehydroascorbic acid.

Excretion

There is a renal threshold for ascorbic acid (Vitamin C); the vitamin is excreted by the kidney in large amounts only when the plasma concentration exceeds this threshold, which is approximately 1.4 mg/100 mL.

Carcinogenicity, mutagenicity, and fertility studies have not been performed with ASCOR.

ASCOR for intravenous use is a colorless to pale yellow solution supplied as:

{ "type": "p", "children": [], "text": "ASCOR for intravenous use is a colorless to pale yellow solution supplied as:" }

{ "type": "ul", "children": [ "NDC 67157-101-50 One 25,000 mg/50 mL (500 mg/mL) Pharmacy Bulk Package vial", "NDC 67157-101-51 Tray pack of twenty five 25,000 mg/50 mL (500 mg/mL) Pharmacy Bulk Package vials" ], "text": "" }

Store in a refrigerator at 2° to 8°C (36° to 46°F).

{ "type": "p", "children": [], "text": "Store in a refrigerator at 2° to 8°C (36° to 46°F)." }

Protect from light. This product contains no preservative. See Dosage and Administration (2.1), for detailed instructions on preparation, dilution, and administration of ASCOR. Excursions to ambient conditions for up to 30 days during storage or shipping are acceptable.

{ "type": "p", "children": [], "text": "Protect from light. This product contains no preservative. See Dosage and Administration (2.1), for detailed instructions on preparation, dilution, and administration of ASCOR. Excursions to ambient conditions for up to 30 days during storage or shipping are acceptable." }

{ "type": "ul", "children": [ "Inform patients that treatment with ASCOR may increase their risk of oxalate nephropathy \n [see Warnings and Precautions \n (5.1)] \n .\n ", "Inform patients that treatment with ASCOR may impact laboratory results, including blood and urine glucose tests, up to 24 hours after infusion \n [see Warnings and Precautions \n (5.3)]. \n \n", "Inform patients with glucose-6-phosphate dehydrogenase deficiency that treatment with ASCOR may increase their risk of hemolysis \n [see Warnings and Precautions \n (5.2)]. \n \n" ], "text": "" }

Manufactured By:

{ "type": "p", "children": [], "text": "Manufactured By:" }

McGuff Pharmaceuticals, Inc., Santa Ana, CA 92704

{ "type": "p", "children": [], "text": "McGuff Pharmaceuticals, Inc., Santa Ana, CA 92704" }

GOZELLIX, after radiolabeling with Ga 68, is indicated for positron emission tomography (PET) of prostate-specific membrane antigen (PSMA) positive lesions in men with prostate cancer:

{ "type": "p", "children": [], "text": "GOZELLIX, after radiolabeling with Ga 68, is indicated for positron emission tomography (PET) of prostate-specific membrane antigen (PSMA) positive lesions in men with prostate cancer:" }

{ "type": "ul", "children": [ "With suspected metastasis who are candidates for initial definitive therapy.", "With suspected recurrence based on elevated serum prostate-specific antigen (PSA) level." ], "text": "" }

After radiolabeling of GOZELLIX, the vial contains Gallium Ga 68 Gozetotide Injection. Handle Gallium Ga 68 Gozetotide Injection with appropriate safety measures to minimize radiation exposure [see Warnings and Precautions (5.2)] . Use waterproof gloves, effective radiation shielding, and other appropriate safety measures when preparing and handling Gallium Ga 68 Gozetotide Injection.

Radiopharmaceuticals should be used by or under the control of healthcare providers who are qualified by specific training and experience in the safe use and handling of radionuclides, and whose experience and training have been approved by the appropriate governmental agency authorized to license the use of radionuclides.

Recommended Dosage

In adults, the recommended amount of radioactivity to be administered for PET is 111 MBq to 259 MBq (3 mCi to 7 mCi) administered as an intravenous bolus injection.

Administration

Instruct patients to drink a sufficient amount of water to ensure adequate hydration prior to administration of Gallium Ga 68 Gozetotide Injection and to continue to drink and void frequently following administration to reduce radiation exposure, particularly during the first hour after administration [see Warnings and Precautions (5.2)] .

Ga 68 Sources and GOZELLIX Carton Configurations

GOZELLIX is supplied as a kit in two different carton configurations, A or B, for preparation of Gallium Ga 68 Gozetotide Injection with eluate from different Ga 68 sources. See Table 1for GOZELLIX carton configurations to be used with different Ga 68 sources.

<div class="scrollingtable"><table width="90%"> <caption> <span>Table 1. Ga 68 Sources and GOZELLIX Carton Configuration</span> </caption> <col align="left" valign="top" width="70%"/> <col align="center" valign="top" width="30%"/> <thead> <tr class="First Last"> <th align="center" class="Lrule Rrule">Ga 68 Source</th><th align="center" class="Rrule">GOZELLIX Carton Configuration to be Used</th> </tr> </thead> <tbody> <tr class="Botrule First"> <td align="left" class="Lrule Rrule">Cyclotron-produced via GE FASTlab</td><td align="center" class="Rrule">A</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">Cyclotron-produced via Alternative Radioisotope Technologies for Medical Science (ARTMS) QUANTM Irradiation System (QIS)</td><td align="center" class="Rrule">A</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">Eckert &amp; Ziegler (EZAG) GalliaPharm Germanium 68/Gallium 68 (Ge 68/Ga 68) generator</td><td align="center" class="Rrule">A</td> </tr> <tr class="Last"> <td align="left" class="Lrule Rrule">IRE ELiT Galli Eo Ge 68/Ga 68 generator</td><td align="center" class="Rrule">B</td> </tr> </tbody> </table></div>

The Ge 68/Ga 68 generators and cyclotron are not supplied with GOZELLIX. Follow the instructions for use provided by the Ge 68/Ga 68 generator or cyclotron manufacturer.

Components of GOZELLIX consist of Vial 1 (Gozetotide), Vial 2A or Vial 2B (Acetate Buffer), and an Ampule (Ascorbic Acid Stabilizer) [see How Supplied/Storage and Handling (16)] .

General Instructions

Procedure for Addition of Ascorbic Acid Stabilizer to Acetate Buffer

Collection of Gallium Ga 68 Chloride Solution

After purification by the FASTlab, the Gallium Ga 68 Chloride solution is passed through a sterile filter and into the cassette product vial automatically by the FASTlab.

When Ga 68 is cyclotron-produced, test for Ga 66 and Ga 67 (with specification of ≤2% combined total) when a new lot of Zn 68 is introduced for manufacturing.

Radiolabeling Procedure

Figure 1: Drug Preparation with Cyclotron-Produced Ga 68 via GE FASTlab Solid or Liquid Target System

Collection of Gallium Ga 68 Chloride Solution

After purification by the ARTMS QIS, the Gallium Ga 68 Chloride solution is passed through a sterile filter and into the cassette product vial automatically by the ARTMS QIS.

When Ga 68 is cyclotron-produced, test for Ga 66 and Ga 67 (with specification of ≤2% combined total) when a new lot of Zn 68 is introduced for manufacturing.

Radiolabeling Procedure

Figure 2: Drug Preparation with Cyclotron-Produced Ga 68 via ARTMS QIS Solid Target System

Follow the generator manufacturers' instructions for generator preparation, controls, and continuous routine elution.

Radiolabeling Procedure

Figure 3: Preparation with EZAG GalliaPharm Generator

Follow the generator manufacturers' instructions for generator preparation, controls, and continuous routine elution.

Radiolabeling Procedure

Figure 4: Preparation with IRE ELiT Galli Eo Generator

Perform the quality controls in Table 2 behind a lead glass shield for radioprotection purposes.

<div class="scrollingtable"><table class="Noautorules" width="90%"> <caption> <span>Table 2: Specifications for Gallium Ga 68 Gozetotide Injection</span> </caption> <col align="left" valign="top" width="40%"/> <col align="left" valign="top" width="30%"/> <col align="left" valign="top" width="30%"/> <thead> <tr class="Botrule Toprule"> <th align="left" class="Lrule Rrule">Test</th><th align="left" class="Rrule">Analytical method</th><th align="left" class="Rrule">Acceptance criteria</th> </tr> </thead> <tbody> <tr class="Botrule"> <td align="left" class="Lrule Rrule">Appearance</td><td align="left" class="Rrule">Visual examination</td><td align="left" class="Rrule">Colorless to slightly yellow solution <br/> Free from visible particles </td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">pH</td><td align="left" class="Rrule">pH-meter or pH-strips</td><td align="left" class="Rrule">4.0 to 5.0</td> </tr> <tr> <td align="left" class="Lrule Rrule">Radiochemical purity</td><td align="left" class="Botrule Rrule" rowspan="2">Instant thin-layer chromatography, silica gel (iTLC SG); <br/> See methods below </td><td align="left" class="Rrule"></td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule"> <ul> <li>Content of gallium Ga 68 gozetotide</li> <li>Content of free and colloidal Ga 68</li> </ul> </td><td align="left" class="Rrule">≥95% <br/> ≤5% </td> </tr> </tbody> </table></div>

Procedure for instant Thin Layer Chromatography (iTLC)

Perform one of the following:

Radiochemical Purity Analysis Using Cutting Technique

<div class="scrollingtable"><table class="Noautorules" width="100%"> <col align="right" valign="middle" width="10%"/> <col align="right" valign="middle" width="4%"/> <col align="center" valign="middle" width="41%"/> <col align="left" valign="middle" width="10%"/> <col align="left" valign="middle" width="35%"/> <tbody class="Headless"> <tr> <td align="left" colspan="5">     <span class="Italics">Radiochemical Purity (%)</span></td> </tr> <tr> <td align="right"></td><td align="right" rowspan="2" valign="middle">  =  </td><td align="center"><span class="Italics">Counts Top Portion</span></td><td align="left" rowspan="2" valign="middle">   × 100</td><td align="left"></td> </tr> <tr> <td align="right"></td><td align="center" class="Toprule"><span class="Italics">Counts from Top Portion + Counts from Bottom Portion</span></td><td align="center"></td> </tr> </tbody> </table></div>

<div class="scrollingtable"><table class="Noautorules" width="90%"> <col align="center" valign="middle" width="100%"/> <tbody class="Headless"> <tr> <td align="center"><span class="Bold">Figure 5: iTLC Strip Preparation and Cutting Points for the Cutting Technique</span></td> </tr> <tr> <td align="center"><img alt="Figure 5" src="/dailymed/image.cfm?name=gozellix-05.jpg&amp;setid=abeab169-e38e-433a-b8a9-f1dab31518c8"/></td> </tr> </tbody> </table></div>

Radiochemical Purity Analysis Using Scanning Technique

Position the patient supine with arms above the head. Begin PET scanning 50 minutes to 100 minutes after the intravenous administration of Gallium Ga 68 Gozetotide Injection. Patients should void immediately prior to image acquisition and image acquisition should begin at the proximal thighs and proceed cranially to the skull base or skull vertex. Adapt imaging technique according to the equipment used and patient characteristics in order to obtain the best image quality possible.

Gallium Ga 68 gozetotide binds to PSMA. Based on the intensity of the signals, PET images obtained using gallium Ga 68 gozetotide 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)] .

Estimated radiation absorbed doses per injected activity for organs and tissues of adult male patients following an intravenous bolus of Gallium Ga 68 Gozetotide Injection are shown in Table 3.

The effective radiation dose resulting from the administration of the maximum recommended activity of 259 MBq (7 mCi) is about 4.4 mSv. The radiation doses for this administered activity to the critical organs, which are the kidneys, urinary bladder, and spleen, are 96.2 mGy, 25.4 mGy, and 16.8 mGy, respectively.

These radiation doses are for Gallium Ga 68 Gozetotide Injection alone. If CT or a transmission source are used for attenuation correction, the radiation dose will increase by an amount that varies by technique.

<div class="scrollingtable"><table width="75%"> <caption> <span>Table 3: Estimated Radiation Absorbed Dose per Injected Activity in Selected Organs and Tissues of Adults after Intravenous Administration of Gallium Ga 68 Gozetotide Injection</span> </caption> <col align="left" valign="top" width="40%"/> <col align="center" valign="top" width="30%"/> <col align="center" valign="top" width="30%"/> <thead> <tr class="Botrule First"> <th align="left" class="Lrule Rrule" rowspan="2" valign="bottom">Organ</th><th align="center" class="Rrule" colspan="2">Absorbed dose (mGy/MBq)</th> </tr> <tr class="Last"> <th align="center" class="Rrule">Mean</th><th align="center" class="Rrule">SD</th> </tr> </thead> <tbody> <tr class="Botrule First"> <td align="left" class="Lrule Rrule">Adrenals</td><td align="center" class="Rrule">0.0156</td><td align="center" class="Rrule">0.0014</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">Brain</td><td align="center" class="Rrule">0.0104</td><td align="center" class="Rrule">0.0011</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">Breasts</td><td align="center" class="Rrule">0.0103</td><td align="center" class="Rrule">0.0011</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">Gallbladder</td><td align="center" class="Rrule">0.0157</td><td align="center" class="Rrule">0.0012</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">Lower Colon</td><td align="center" class="Rrule">0.0134</td><td align="center" class="Rrule">0.0009</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">Small Intestine</td><td align="center" class="Rrule">0.014</td><td align="center" class="Rrule">0.002</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">Stomach</td><td align="center" class="Rrule">0.0129</td><td align="center" class="Rrule">0.0008</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">Heart</td><td align="center" class="Rrule">0.012</td><td align="center" class="Rrule">0.0009</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">Kidneys</td><td align="center" class="Rrule">0.3714</td><td align="center" class="Rrule">0.0922</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">Liver</td><td align="center" class="Rrule">0.0409</td><td align="center" class="Rrule">0.0076</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">Lungs</td><td align="center" class="Rrule">0.0111</td><td align="center" class="Rrule">0.0007</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">Muscle</td><td align="center" class="Rrule">0.0103</td><td align="center" class="Rrule">0.0003</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">Pancreas</td><td align="center" class="Rrule">0.0147</td><td align="center" class="Rrule">0.0009</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">Red Marrow</td><td align="center" class="Rrule">0.0114</td><td align="center" class="Rrule">0.0016</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">Skin</td><td align="center" class="Rrule">0.0091</td><td align="center" class="Rrule">0.0003</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">Spleen</td><td align="center" class="Rrule">0.065</td><td align="center" class="Rrule">0.018</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">Testes</td><td align="center" class="Rrule">0.0111</td><td align="center" class="Rrule">0.0006</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">Thymus</td><td align="center" class="Rrule">0.0105</td><td align="center" class="Rrule">0.0006</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">Thyroid</td><td align="center" class="Rrule">0.0104</td><td align="center" class="Rrule">0.0006</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">Urinary Bladder</td><td align="center" class="Rrule">0.0982</td><td align="center" class="Rrule">0.0286</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">Total Body</td><td align="center" class="Rrule">0.0143</td><td align="center" class="Rrule">0.0013</td> </tr> <tr class="Last"> <td align="left" class="Lrule Rrule"><span class="Bold">Effective Dose (mSv/MBq)</span></td><td align="center" class="Rrule"><span class="Bold">0.0169</span></td><td align="center" class="Rrule"><span class="Bold">0.0015</span></td> </tr> </tbody> </table></div>

Kit for the preparation of Gallium Ga 68 Gozetotide Injection contains:

{ "type": "p", "children": [], "text": "Kit for the preparation of Gallium Ga 68 Gozetotide Injection contains:" }

{ "type": "ul", "children": [ "Vial 1 (Gozetotide): 25 mcg of gozetotide as a white to off-white lyophilized powder in a multiple-dose vial", "Vial 2A (2.5 mL) or Vial 2B (6.4 mL) (Acetate Buffer): 150 mg anhydrous sodium acetate as a sterile clear colorless solution\n \n \nVial 2A in Configuration A for use with cyclotron-produced Ga 68 via GE FASTlab or ARTMS QIS, or EZAG Gallia Pharm generator\nVial 2B in Configuration B for use with IRE EliT Galli Eo generator\n\n", "Ampule (Ascorbic Acid Stabilizer): 500 mg/2 mL (250 mg/mL) of ascorbic acid (USP injection grade) as a sterile clear colorless solution" ], "text": "" }

After radiolabeling with Ga 68, Vial 1 contains up to 18,500 MBq (500 mCi) of Gallium Ga 68 Gozetotide Injection in 10 mL at calibration date and time as a clear, colorless to slightly yellow solution in a multiple-dose vial.

{ "type": "p", "children": [], "text": "After radiolabeling with Ga 68, Vial 1 contains up to 18,500 MBq (500 mCi) of Gallium Ga 68 Gozetotide Injection in 10 mL at calibration date and time as a clear, colorless to slightly yellow solution in a multiple-dose vial." }

None

{ "type": "p", "children": [], "text": "None" }

Image interpretation errors can occur with GOZELLIX PET. A negative image does not rule out the presence of prostate cancer and a positive image does not confirm the presence of prostate cancer. Gallium Ga 68 gozetotide uptake is not specific for prostate cancer and may occur with other types of cancer as well as non-malignant processes such as Paget's disease, fibrous dysplasia, and osteophytosis. The performance of GOZELLIX for imaging of biochemically recurrent prostate cancer seems to be affected by serum PSA levels and by site of disease. The performance of GOZELLIX for imaging of metastatic pelvic lymph nodes prior to initial definitive therapy seems to be affected by Gleason score [see Clinical Studies (14.1, 14.2)] .

Clinical correlation, which may include histopathological evaluation of the suspected prostate cancer site, is recommended.

Gallium Ga 68 gozetotide contributes to a patient's overall long-term cumulative radiation exposure. Long-term cumulative radiation exposure is associated with an increased risk for cancer. Ensure safe handling to minimize radiation exposure to the patient and health care providers. Advise patients to hydrate before and after administration and to void frequently after administration [see Dosage and Administration (2.1, 2.3)] .

Ascorbic Acid Stabilizer contains sodium metabisulfite, a sulfite that may cause allergic-type reactions including anaphylactic symptoms and life-threatening or less severe asthmatic episodes in certain susceptible people. The overall prevalence of sulfite sensitivity in the general population is unknown and probably low. Sulfite sensitivity is seen more frequently in asthmatic than in non-asthmatic people.

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 GOZELLIX has been established based on two prospective studies of another formulation of gallium Ga 68 gozetotide in patients with prostate cancer [see Clinical Studies (14.1, 14.2)] . Below is a display of the adverse reactions in these studies.

The safety of gallium Ga 68 gozetotide was evaluated in 960 patients in the PSMA-PreRP and PSMA-BCR studies, each receiving one dose of gallium Ga 68 gozetotide. The average injected activity was 188.7 ± 40.7 MBq (5.1 ± 1.1 mCi) [see Clinical Studies (14.1, 14.2)] . The most commonly reported adverse reactions were nausea, diarrhea, and dizziness, occurring at a rate of <1%.

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, can result in changes in uptake of gallium Ga 68 gozetotide in prostate cancer. The effect of these therapies on performance of gallium Ga 68 gozetotide PET has not been established.

Risk Summary

GOZELLIX is not indicated for use in females. There are no available data with gallium Ga 68 gozetotide injection use in pregnant women to evaluate for a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes. All radiopharmaceuticals, including GOZELLIX, have the potential to cause fetal harm depending on the fetal stage of development and the magnitude of the radiation dose. Animal reproduction studies have not been conducted with gallium Ga 68 gozetotide.

Risk Summary

GOZELLIX is not indicated for use in females. There are no data on the presence of gallium Ga 68 gozetotide in human milk, the effect on the breastfed infant, or the effect on milk production.

The safety and effectiveness of gallium Ga 68 gozetotide in pediatric patients have not been established.

The efficacy of gallium Ga 68 gozetotide PET in geriatric patients with prostate cancer is based on data from two prospective studies [see Clinical Studies (14.1, 14.2)].

Of the total number of subjects in the PSMA-PreRP and PSMA-BCR studies, 691 of 960 (72%) patients were 65 years of age and older while 195 (20%) were 75 years of age and older.

The efficacy and safety profiles of gallium Ga 68 gozetotide appear similar in younger adult and geriatric patients with prostate cancer and other reported clinical experience has not identified differences in responses between the elderly and younger adult patients.

In the event of an overdose of gallium Ga68 gozetotide, 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 given to the patient should be made.

{ "type": "p", "children": [], "text": "In the event of an overdose of gallium Ga68 gozetotide, 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 given to the patient should be made." }

GOZELLIX (kit for the preparation of gallium Ga 68 gozetotide injection), after radiolabeling with Ga 68, is a radioactive diagnostic agent for intravenous use. Gozetotide is also known as PSMA-11.

Gallium Ga 68 gozetotide is a radioconjugate composed of a human prostate specific membrane antigen (PSMA)-targeting ligand peptide conjugated via the acyclic radiometal chelator, N,N'-bis [2-hydroxy-5-(carboxyethyl)benzyl] ethylenediamine-N,N'-diacetic acid (HBED-CC) to the radioisotope Ga 68. The amino acid sequence of the gozetotide peptide is Glu-NH-CO-NH-Lys(Ahx), (Ahx = 6-aminohexanoic acid). Gallium Ga 68 gozetotide has a molecular weight of 1011.9 g/mol and its chemical structure is shown in Figure 6.

Figure 6: Chemical Structure of Gallium Ga 68 Gozetotide

Kit Characteristics

GOZELLIX is supplied as a kit which contains the non-radioactive ingredients needed to produce Gallium Ga 68 Gozetotide Injection. There are two configurations, A or B, available to allow preparation of Gallium Ga 68 Gozetotide Injection using Ga 68 from different generator or cyclotron sources. Each configuration consists of gozetotide (Vial 1), acetate buffer (Vial 2A or Vial 2B), and ascorbic acid stabilizer (Ampule).

The prepared Gallium Ga 68 Gozetotide Injection is a sterile, pyrogen free, clear, colorless to slightly yellow, buffered solution containing up to 18,500 MBq (500 mCi) of gallium Ga 68 gozetotide in 10 mL with a pH between 4.0 to 5.0.

Gallium-68 (Ga 68) decays with a half-life of 68 minutes to stable zinc-68. Table 4, Table 5, and Table 6 display the principal radiation emission data, radiation attenuation by lead shielding, and physical decay of Ga 68.

<div class="scrollingtable"><table width="60%"> <caption> <span>Table 4: Principal Radiation Emission Data (&gt;1%) for Ga 68</span> </caption> <col align="left" valign="top" width="33%"/> <col align="left" valign="top" width="33%"/> <col align="left" valign="top" width="34%"/> <thead> <tr class="First Last"> <th align="left" class="Lrule Rrule">Radiation/ Emission</th><th align="left" class="Rrule">% Disintegration</th><th align="left" class="Rrule">Mean Energy (MeV)</th> </tr> </thead> <tbody> <tr class="Botrule First"> <td align="left" class="Lrule Rrule">beta+</td><td align="left" class="Rrule">88%</td><td align="left" class="Rrule">0.8360</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">beta+</td><td align="left" class="Rrule">1.1%</td><td align="left" class="Rrule">0.3526</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">gamma</td><td align="left" class="Rrule">178%</td><td align="left" class="Rrule">0.5110</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">gamma</td><td align="left" class="Rrule">3.0%</td><td align="left" class="Rrule">1.0770</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">X-ray</td><td align="left" class="Rrule">2.8%</td><td align="left" class="Rrule">0.0086</td> </tr> <tr class="Last"> <td align="left" class="Lrule Rrule">X-ray</td><td align="left" class="Rrule">1.4%</td><td align="left" class="Rrule">0.0086</td> </tr> </tbody> </table></div>

<div class="scrollingtable"><table width="45%"> <caption> <span>Table 5: Radiation Attenuation of 511 keV Photons by Lead (Pb) Shielding</span> </caption> <col align="left" valign="top" width="50%"/> <col align="left" valign="top" width="50%"/> <thead> <tr class="First Last"> <th align="left" class="Lrule Rrule">Shield Thickness (Pb) mm</th><th align="left" class="Rrule">Coefficient of Attenuation</th> </tr> </thead> <tbody> <tr class="Botrule First"> <td align="left" class="Lrule Rrule">6</td><td align="left" class="Rrule">0.5</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">12</td><td align="left" class="Rrule">0.25</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">17</td><td align="left" class="Rrule">0.1</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">34</td><td align="left" class="Rrule">0.01</td> </tr> <tr class="Last"> <td align="left" class="Lrule Rrule">51</td><td align="left" class="Rrule">0.001</td> </tr> </tbody> </table></div>

<div class="scrollingtable"><table width="45%"> <caption> <span>Table 6: Physical Decay Chart for Ga 68</span> </caption> <col align="left" valign="top" width="50%"/> <col align="left" valign="top" width="50%"/> <thead> <tr class="First Last"> <th align="left" class="Lrule Rrule">Minutes</th><th align="left" class="Rrule">Fraction Remaining</th> </tr> </thead> <tbody> <tr class="Botrule First"> <td align="left" class="Lrule Rrule">0</td><td align="left" class="Rrule">1</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">15</td><td align="left" class="Rrule">0.858</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">30</td><td align="left" class="Rrule">0.736</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">60</td><td align="left" class="Rrule">0.541</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">90</td><td align="left" class="Rrule">0.398</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">120</td><td align="left" class="Rrule">0.293</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">180</td><td align="left" class="Rrule">0.158</td> </tr> <tr class="Last"> <td align="left" class="Lrule Rrule">360</td><td align="left" class="Rrule">0.025</td> </tr> </tbody> </table></div>

Gallium Ga 68 gozetotide binds to PSMA. It binds to cells that express PSMA, including malignant prostate cancer cells, which usually overexpress PSMA. Gallium-68 is a β+ emitting radionuclide that allows positron emission tomography.

The relationship between gallium Ga 68 gozetotide plasma concentrations and successful imaging was not explored in clinical trials.

Distribution

Intravenously injected gallium Ga 68 gozetotide is cleared from the blood and is accumulated preferentially in the liver (15%), kidneys (7%), spleen (2%), and salivary glands (0.5%). Gallium Ga 68 gozetotide uptake is also seen in the adrenals and prostate. There is no uptake in the cerebral cortex or in the heart, and usually lung uptake is low.

Elimination

A total of 14% of the injected dose is excreted in urine in the first 2 hours post-injection.

No long-term animal studies were performed to evaluate the carcinogenicity potential of gallium Ga 68 gozetotide.

The efficacy of GOZELLIX for PET of PSMA-positive lesions in men with prostate cancer with suspected metastasis who are candidates for initial definitive therapy has been established based on a study of another formulation of gallium Ga 68 gozetotide. Below is a display of the results of the prospective, open label study PSMA-PreRP (NCT03368547 and NCT02919111).

This two-center study enrolled 325 patients with biopsy-proven prostate cancer who were considered candidates for prostatectomy and pelvic lymph node dissection. All enrolled patients met at least one of the following criteria: serum prostate-specific antigen (PSA) of at least 10 ng/mL, tumor stage cT2b or greater, or Gleason score greater than 6. Each patient received a single gallium Ga 68 gozetotide PET/CT or PET/MR from mid-thigh to skull base.

A total of 123 patients (38%) proceeded to standard-of-care prostatectomy and template pelvic lymph node dissection and had sufficient histopathology data for evaluation (evaluable patients). Three members of a pool of six central readers independently interpreted each PET scan for the presence of abnormal gallium Ga 68 gozetotide uptake in pelvic lymph nodes located in the common iliac, external iliac, internal iliac, and obturator subregions bilaterally as well as in any other pelvic location. The readers were blinded to all clinical information except for the history of prostate cancer prior to definitive treatment. Extrapelvic sites and the prostate gland itself were not analyzed in this study. For each patient, gallium Ga 68 gozetotide PET results and reference standard histopathology obtained from dissected pelvic lymph nodes were compared by region (left hemipelvis, right hemipelvis, and other).

For the 123 evaluable patients, the mean age was 65 years (range 45 to 76 years), and 89% were white. The median serum PSA was 11.8 ng/mL. The summed Gleason score was 7 for 44%, 8 for 20%, and 9 for 31% of the patients, with the remainder of the patients having Gleason scores of 6 or 10.

Table 7 compares majority PET reads to pelvic lymph node histopathology results at the patient-level with region matching, such that at least one true positive region defines a true positive patient. As shown, approximately 24% of subjects studied were found to have pelvic nodal metastases based on histopathology (95% confidence interval: 17%, 32%).

<div class="scrollingtable"><table width="80%"> <caption> <span>Table 7: Patient-Level Performance of Gallium Ga 68 Gozetotide PET for Detection of Pelvic Lymph Node Metastasis <a class="Sup" href="#footnote-1" name="footnote-reference-1">*</a>in the PSMA-PreRP Study (n=123) </span> </caption> <col align="center" valign="bottom" width="12%"/> <col align="center" valign="bottom" width="22%"/> <col align="center" valign="bottom" width="22%"/> <col align="center" valign="bottom" width="22%"/> <col align="center" valign="bottom" width="22%"/> <thead> <tr class="Botrule First"> <th align="center" class="Lrule Rrule" colspan="2" rowspan="2"></th><th align="center" class="Rrule" colspan="2">Histopathology</th><th align="center" class="Rrule" rowspan="2" valign="top">Predictive value <a class="Sup" href="#footnote-2" name="footnote-reference-2">†</a> <br/> (95% CI) </th> </tr> <tr class="Last"> <th align="center" class="Rrule">Positive</th><th align="center" class="Rrule">Negative</th> </tr> </thead> <tfoot> <tr> <td align="left" colspan="5"> <dl class="Footnote"> <dt> <a href="#footnote-reference-1" name="footnote-1">*</a> </dt> <dd>with region matching where at least one true positive region defines a true positive patient</dd> <dt> <a href="#footnote-reference-2" name="footnote-2">†</a> </dt> <dd>PPV: positive predictive value, NPV: negative predictive value</dd> </dl> </td> </tr> </tfoot> <tbody> <tr class="Botrule First"> <td align="center" class="Lrule Rrule" rowspan="2" valign="middle"><span class="Bold">PET scan</span></td><td align="left" class="Rrule"><span class="Bold">Positive</span></td><td align="center" class="Rrule">14</td><td align="center" class="Rrule">9</td><td align="center" class="Rrule">PPV <br/> 61% (41%, 81%) </td> </tr> <tr class="Botrule"> <td align="left" class="Rrule"><span class="Bold">Negative</span></td><td align="center" class="Rrule">16</td><td align="center" class="Rrule">84</td><td align="center" class="Rrule">NPV <br/> 84% (79%, 91%) </td> </tr> <tr> <td align="center" class="Botrule Lrule"> </td><td align="center" class="Botrule Rrule"></td><td align="center" class="Botrule Rrule"></td><td align="center" class="Botrule Rrule"></td><td align="center" class="Rrule"></td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule" colspan="2"><span class="Bold">Total</span></td><td align="center" class="Botrule Rrule">30</td><td align="center" class="Botrule Rrule">93</td><td align="center" class="Rrule"></td> </tr> <tr> <td align="center" class="Botrule Lrule"> </td><td align="center" class="Botrule Rrule"></td><td align="center" class="Botrule Rrule"></td><td align="center" class="Botrule Rrule"></td><td align="center" class="Rrule"></td> </tr> <tr class="Last"> <td align="left" class="Lrule Rrule" colspan="2"><span class="Bold">Diagnostic performance <br/> (95% CI) </span></td><td align="center" class="Rrule">Sensitivity <br/> 47% (29%, 65%) </td><td align="center" class="Rrule">Specificity <br/> 90% (84%, 96%) </td><td align="center" class="Rrule"></td> </tr> </tbody> </table></div>

Among the pool of six readers, sensitivity ranged from 36% to 60%, specificity from 83% to 96%, positive predictive value from 38% to 80%, and negative predictive value from 80% to 88%. In an exploratory subgroup analysis based on summed Gleason score, there was a numerical trend toward more true positives in patients with Gleason score of 8 or higher compared to those with Gleason score of 7 or lower.

An exploratory analysis was performed to estimate the sensitivity and specificity for pelvic nodal metastasis detection in all scanned patients, including the patients who were lacking histopathology reference standard. An imputation method was used based on patient-specific factors. This exploratory analysis resulted in an imputed sensitivity of 47%, with a 95% confidence interval ranging from 38% to 55%, and an imputed specificity of 74%, with a 95% confidence interval ranging from 68% to 80% for all patients imaged with gallium Ga 68 gozetotide PET.

The efficacy of GOZELLIX for PET of PSMA-positive lesions in men with prostate cancer with suspected recurrence based on elevated serum PSA level has been established based on a study of another formulation of gallium Ga 68 gozetotide. Below is a display of the results of the prospective, open label study PSMA-BCR (NCT02940262 and NCT02918357).

This two-center study enrolled 635 patients with biochemical evidence of recurrent prostate cancer after definitive therapy, defined by serum PSA of >0.2 ng/mL more than 6 weeks after prostatectomy or by an increase in serum PSA of at least 2 ng/mL above nadir after definitive radiotherapy. All patients received a single gallium Ga 68 gozetotide PET/CT or PET/MR from mid-thigh to skull base. Three members of a pool of nine independent central readers evaluated each scan for the presence and regional location (20 subregions grouped into four regions) of abnormal gallium Ga 68 gozetotide uptake suggestive of recurrent prostate cancer. The readers were blinded to all clinical information other than type of primary therapy and most recent serum PSA level.

A total of 469 patients (74%) had at least one positive region detected by gallium Ga 68 gozetotide PET majority read. The distribution of gallium Ga 68 gozetotide PET positive regions was 34% bone, 25% prostate bed, 25% pelvic lymph node, and 17% extrapelvic soft tissue. Two hundred and ten patients had composite reference standard information collected in a PET positive region (evaluable patients), consisting of at least one of the following: histopathology, imaging (bone scintigraphy, CT, or MRI) acquired at baseline or within 12 months after gallium Ga 68 gozetotide PET, or serial serum PSA.

Composite reference standard information for gallium Ga 68 gozetotide PET negative regions was not systematically collected in this study.

In the 210 evaluable patients, the mean age was 70 years (range 49 to 88 years) and 82% were 65 years of age or older. White patients made up 90% of the group. The median serum PSA was 3.6 ng/mL. Prior treatment included radical prostatectomy in 64% and radiotherapy in 73%.

Of the 210 evaluable patients, 192 patients (91%) were found to be true positive in one or more regions against the composite reference standard (95% confidence interval: 88%, 95%). Among the pool of nine readers used in the study, the proportion of patients who were true positive in one or more regions ranged from 82% to 97%. The prostate bed had the lowest proportion of true positive results at the region-level (76% versus 96% for non-prostate regions).

An exploratory analysis was also performed in which gallium Ga 68 gozetotide PET positive patients who lacked reference standard information were imputed using an estimated likelihood that at least one location-matched PET positive lesion was reference standard positive based on patient-specific factors. In this exploratory analysis, 340 of 475 patients (72%) were imputed as true positive in one or more regions (95% confidence interval: 68%, 76%).

In another exploratory analysis using the same imputation approach for PET positive patients who lacked reference standard information, 340 of 635 patients (54%) were correctly detected as true positive (95% confidence interval: 50%, 57%) among all BCR patients who received a PET scan, whether it was read as positive or negative.

The likelihood of identifying a gallium Ga 68 gozetotide PET positive lesion in this study increased with higher serum PSA level. Table 8 shows the patient-level gallium Ga 68 gozetotide PET results stratified by serum PSA level. The mean time between PSA measurement and PET scan was 40 days with a range of 0 to 367 days. Percent PET positivity was calculated as the proportion of patients with a positive gallium Ga 68 gozetotide 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 the absence of composite reference standard data.

<div class="scrollingtable"><table class="Noautorules" width="90%"> <caption> <span>Table 8: Patient-Level Gallium Ga 68 Gozetotide PET Results and Percent PET Positivity Stratified by Serum PSA Level in the PSMA-BCR Study (n=628) <a class="Sup" href="#footnote-3" name="footnote-reference-3">*</a></span> </caption> <col align="left" valign="top" width="20%"/> <col align="center" valign="top" width="8%"/> <col align="center" valign="top" width="5%"/> <col align="center" valign="top" width="5%"/> <col align="center" valign="top" width="12%"/> <col align="center" valign="top" width="20%"/> <col align="center" valign="top" width="30%"/> <thead> <tr class="Botrule Toprule"> <th align="left" class="Lrule Rrule" rowspan="3">PSA (ng/mL)</th><th align="center" class="Rrule" colspan="4">PET positive patients</th><th align="center" class="Rrule" rowspan="3">PET negative patients</th><th align="center" class="Rrule" rowspan="3">Percent PET positivity <a class="Sup" href="#footnote-4" name="footnote-reference-4">†</a> <br/> (95% CI) </th> </tr> <tr class="Botrule"> <th align="center" class="Rrule" rowspan="2">Total</th><th align="center" class="Rrule">TP <a class="Sup" href="#footnote-5" name="footnote-reference-5">‡</a></th><th align="center" class="Rrule">FP <a class="Sup" href="#footnote-5">‡</a></th><th align="center" class="Rrule" rowspan="2">Without reference standard</th> </tr> <tr> <th align="center" class="Botrule Rrule" colspan="2">With reference standard</th> </tr> </thead> <tfoot> <tr> <td align="left" colspan="7"> <dl class="Footnote"> <dt> <a href="#footnote-reference-3" name="footnote-3">*</a> </dt> <dd>7 patients were excluded from this table due to protocol deviations</dd> <dt> <a href="#footnote-reference-4" name="footnote-4">†</a> </dt> <dd>Percent PET positivity = PET positive patients/total patients scanned</dd> <dt> <a href="#footnote-reference-5" name="footnote-5">‡</a> </dt> <dd>TP: true positive, FP: false positive</dd> </dl> </td> </tr> </tfoot> <tbody> <tr class="Botrule"> <td align="left" class="Lrule Rrule" rowspan="2">&lt;0.5</td><td align="center" class="Rrule" rowspan="2">48</td><td align="center" class="Rrule">11</td><td align="center" class="Rrule">1</td><td align="center" class="Rrule" rowspan="2">36</td><td align="center" class="Rrule" rowspan="2">87</td><td align="center" class="Rrule" rowspan="2">36% <br/> (27%, 44%) </td> </tr> <tr class="Botrule"> <td align="center" class="Rrule" colspan="2">12</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule" rowspan="2">≥0.5 and &lt;1</td><td align="center" class="Rrule" rowspan="2">44</td><td align="center" class="Rrule">15</td><td align="center" class="Rrule">3</td><td align="center" class="Rrule" rowspan="2">26</td><td align="center" class="Rrule" rowspan="2">35</td><td align="center" class="Rrule" rowspan="2">56% <br/> (45%, 67%) </td> </tr> <tr class="Botrule"> <td align="center" class="Rrule" colspan="2">18</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule" rowspan="2">≥1 and &lt;2</td><td align="center" class="Rrule" rowspan="2">71</td><td align="center" class="Rrule">29</td><td align="center" class="Rrule">1</td><td align="center" class="Rrule" rowspan="2">41</td><td align="center" class="Rrule" rowspan="2">15</td><td align="center" class="Rrule" rowspan="2">83% <br/> (75%, 91%) </td> </tr> <tr class="Botrule"> <td align="center" class="Rrule" colspan="2">30</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule" rowspan="2">≥2</td><td align="center" class="Rrule" rowspan="2">299</td><td align="center" class="Rrule">137</td><td align="center" class="Rrule">13</td><td align="center" class="Rrule" rowspan="2">149</td><td align="center" class="Rrule" rowspan="2">29</td><td align="center" class="Rrule" rowspan="2">91% <br/> (88%, 94%) </td> </tr> <tr class="Botrule"> <td align="center" class="Rrule" colspan="2">150</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule" rowspan="2">Total</td><td align="center" class="Rrule" rowspan="2">462</td><td align="center" class="Rrule">192</td><td align="center" class="Rrule">18</td><td align="center" class="Rrule" rowspan="2">252</td><td align="center" class="Rrule" rowspan="2">166</td><td align="center" class="Rrule" rowspan="2">74% <br/> (70%, 77%) </td> </tr> <tr class="Botrule"> <td align="center" class="Rrule" colspan="2">210</td> </tr> </tbody> </table></div>

Storage and Handling

Store GOZELLIX refrigerated upright in the original packaging at 2° to 8°C (36° to 46°F). Do not freeze.

After radiolabeling, keep Gallium Ga 68 Gozetotide Injection upright with appropriate shielding to protect from radiation at room temperature (25°C (77°F); excursions permitted to 15°C to 30°C (59°F to 86°F)). Use Gallium Ga 68 Gozetotide Injection within the time frames described in Table 9 below.

<div class="scrollingtable"><table width="60%"> <caption> <span>Table 9: Shelf Life Per Activity of Gallium Ga 68 Gozetotide Injection</span> </caption> <col align="left" valign="middle" width="50%"/> <col align="center" valign="middle" width="50%"/> <thead> <tr class="First Last"> <th align="center" class="Lrule Rrule">Activity</th><th align="center" class="Rrule">Shelf Life</th> </tr> </thead> <tbody> <tr class="Botrule First"> <td align="left" class="Lrule Rrule">Less than 2,590 MBq (70 mCi)</td><td align="center" class="Rrule">4 hours</td> </tr> <tr class="Last"> <td align="left" class="Lrule Rrule">2,590 MBq to 18,500 MBq (70 mCi to 500 mCi)</td><td align="center" class="Rrule">6 hours</td> </tr> </tbody> </table></div>

Dispose of the product in accordance with all federal, state, and local laws and institutional requirements.

This preparation is approved for use by persons under license by the Nuclear Regulatory Commission or the relevant regulatory authority of an Agreement State.

Adequate Hydration

Instruct patients to drink a 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 Gallium Ga 68 Gozetotide Injection, in order to reduce radiation exposure [see Dosage and Administration (2.3)and Warnings and Precautions (5.2)] .

Manufactured for: Telix Innovations SA rue de Hermée 255 à 4040 Herstal, Belgium

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For optional information on GOZELLIX, see www.gozellix.com.

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GOZELLIX is a registered trademark of Telix Pharmaceuticals Limited Copyright © 2025 Telix Innovations SA All rights reserved.

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Rx Only

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NDC 84552-500-25

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Gozellix™ kit for the preparation of gallium Ga 68 gozetotide injection

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25 mcg/vial gozetotide

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Kit for the preparation of gallium Ga 68 gozetotide injection is supplied as multiple dose kit containing:

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2D

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For Intravenous Use Only

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Multiple-Dose Kit

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CONFIGURATION A

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Configuration A is for use with the EZAG GalliaPharm ®or Ga 68 produced by cyclotron using GE liquid or solid target, or ARTMS solid target.

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Rx Only

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NDC 84552-500-64

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Gozellix™ kit for the preparation of gallium Ga 68 gozetotide injection

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25 mcg/vial gozetotide

{ "type": "p", "children": [], "text": "25 mcg/vial gozetotide" }

Kit for the preparation of gallium Ga 68 gozetotide injection is supplied as multiple dose kit containing:

{ "type": "p", "children": [], "text": "Kit for the preparation of gallium Ga 68 gozetotide \n injection is supplied as multiple dose kit containing:\n " }

{ "type": "ul", "children": [ "Prescribing Information", "Diagnostic label", "Vial 1 (Gozetotide vial) contains 25 mcg \n gozetotide vial\n ", "Vial 2B (Acetate Buffer Vial) contains \n acetate buffer\n ", "Ampule (Ascorbic Acid stabilizer)" ], "text": "" }

2D

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For Intravenous Use Only

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Multiple-Dose Kit

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CONFIGURATION B

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Configuration B is for use with the IRE ELiT Galli Eo ®.

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